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in Brazil&#41; affects exclusively the skin of young adults&#44; with anti-Dsg1 production&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Dsg1 and 3 are transmembrane proteins of 160kDa and 130kDa&#44; respectively&#44; expressed by genes located on chromosome 18&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Dsgs compensation theory explains the level of intraepidermal acantholysis in pemphigus&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Anti-Dsg1 antibodies in PF cause subgranular acantholysis&#44; as Dsg1 is expressed more intensily in the upper layers of the epidermis&#46; Anti-Dsg3 antibodies cause suprabasal acantholysis&#44; as Dsg3 is most often expressed in the lower layers of the epidermis&#44; and in all epithelial layers in the mucous membranes&#46; Moreover&#44; as there is a lower expression of Dsg1 in the mucosa&#44; it is not affected by anti-Dsg1 antibodies in PF&#44; as Dsg3 compensates for epithelial cell cohesion in the mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Subsequently&#44; the hypothesis of Dsgs compensation&#44; to explain the level of cleavage of epidermal acantholysis related to the production of anti-Dsg1 and 3&#44; started to be discussed again&#44; since exclusively suprabasal acantholysis in PV would not be explained in the mucocutaneous form&#44; when anti-Dsg1 is also present&#46; Other target molecules of epidermal adhesion are now identified in the pathogenesis of pemphigus&#44; as well as mitochondrial proteins&#44; cholinergic receptors&#44; and other molecules&#44; which act synergistically with anti-Dsg1 and Dsg3 antibodies in epidermal acantholysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;18</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">As both PV and PF are prevalent in southeastern Brazil&#44; there is an opportunity for outpatient follow-up of a large series of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> In the PF series&#44; over a 25-year period&#44; it was observed that 6&#44;64 &#37; of the patients&#44; in addition to being positive for anti-Dsg1&#44; also had reactive titers to Dsg3 in the ELISA test&#44; without&#44; however&#44; showing a phenotype of mucosal lesions&#46; Therefore&#44; we aimed to analyze clinical-laboratory data in the group of patients with PF and reactivity to Dsg3 &#40;PF-anti-Dsg3&#43;&#41;&#46; For this purpose&#44; three groups were compared&#58; PF-anti-Dsg3&#43;&#44; PF with anti-Dsg3 negativity and treatment-na&#239;ve &#91;PF-anti-Dsg3&#40;&#727;&#41;&#93;&#44; and treatment-na&#239;ve PV&#46; For specific purposes&#44; the following were evaluated&#58; &#40;i&#41; Demographic and clinical data&#59; &#40;ii&#41; Temporal evolution of anti-Dsg1 and 3 titers by ELISA and identification of Dsg1 and 3 by immunoblotting &#40;IB&#41; in the PF-anti-Dsg3&#43; group&#59; and &#40;iii&#41; Expression of Dsg1 and 3 in paraffin-embedded skin biopsies by immunohistochemistry &#40;IHC&#41; and &#40;iv&#41; typification of <span class="elsevierStyleItalic">HLA-DRB1</span> alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3&#40;-&#41; groups&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is a comparative analytical study of three groups&#46; The sample bank of the Dermatology Laboratory&#44; Hospital das Cl&#237;nicas&#44; FMRP-USP&#44; has the approval of the Research Ethics Committee &#40;HCRP Process number 3605&#47;2006&#41;&#46; Patients and control individuals signed the free and informed consent form at the time of sample collection&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Case series</span><p id="par0025" class="elsevierStylePara elsevierViewall">It consisted of 80 patients&#58; 16 PF-anti-Dsg3&#43;&#44; 42 PF-anti-Dsg3&#40;-&#41; and 22 PV cases&#46; The clinical findings were confirmed by histopathological examination and by direct immunofluorescence &#40;DIF&#41; and&#47;or indirect immunofluorescence &#40;IIF&#41;&#46; Demographic&#44; clinical and laboratory data &#40;anti-Dsg1 and Dsg3 by ELISA and HLA alleles&#41; were obtained from data recorded at the Laboratory of Dermatology&#46; In the PF-anti-Dsg3&#43; group&#44; three &#40;20&#37;&#41; of the 15 patients &#40;with information about treatment&#41; were untreated at the time of blood collection&#44; while 42 of the PF-anti-Dsg3&#40;-&#41; patients and 22&#8239;PV were all treatment-na&#239;ve&#46; Immunoblotting &#40;IB&#41; assays were performed with 12 &#40;75&#37;&#41; of the 16 serum samples from the PF-anti-Dsg3&#43; group&#44; with some patients having more than one sample analyzed&#44; collected at different times&#46; IHC was performed on sections from the paraffin blocks of four patients from the PF-anti-Dsg3&#43; group and one from the PF-anti-Dsg3&#40;-&#41; group&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">ELISA for the detection of IgG antibodies against Dsg1 and 3</span><p id="par0030" class="elsevierStylePara elsevierViewall">The manufacturers recommendations were followed&#46; Values &#8805; 20&#8239;U&#47;mL&#44; between 9&#8210;20&#8239;U&#47;mL and &#60; 9&#8239;U&#47;mL were considered positive&#44; indeterminate and negative&#44; respectively &#40;MBL&#44; Nagoya&#44; Japan&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">IB with human epidermis extract and patient serum</span><p id="par0035" class="elsevierStylePara elsevierViewall">Briefly&#44; skin fragments were incubated for 48&#8239;h in PBS with EDTA &#40;Merck&#41; and PMSF &#40;Sigma-Aldrich&#41; to separate the epidermis from the dermis&#46; Protein extraction from the epidermis was carried out with a Tris-HCL&#44; SDS&#44; 2-mercaptoethanol solution&#44; and then an EDTA&#44; PMSF and proteinase inhibitor cocktail &#40;Sigma-Aldrich&#41; were added&#46; After the electrophoretic run&#44; the polyacrylamide gel was assembled in a sandwich with a 0&#46;45&#8239;&#181;m nitrocellulose membrane &#40;BioRad&#41; for protein transfer&#46; After blocking with 3&#37; skimmed milk in TBS&#44; and consecutive washings&#44; the serum samples &#40;1&#58;20&#41; were incubated on nitrocellulose strips&#44; followed by incubation with anti-human HRP IgG secondary antibody &#40;BioRad&#41;&#46; After washing&#44; color reagent &#40;Color-Plus HRP&#44; BioRad&#41; was added for colorimetric development&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Expression of Dsgs1 and 3 in paraffin-embedded samples with IHC</span><p id="par0040" class="elsevierStylePara elsevierViewall">For IHC assays&#44; the manufacturers recommendations were followed &#40;HRP-Polymer MACH1&#44; Biocare Medical&#44; Concord&#44; CA&#44; USA&#41;&#46; Briefly&#44; 5&#956;m sections were obtained and after antigen retrieval in citrate&#44; inhibition of endogenous peroxidase and use of a blocking solution&#44; were incubated with anti-Dsg1 and 3 monoclonal antibodies produced in mice &#40;Abcam&#44; MA&#44; USA&#41;&#46; After washing and incubation with Probe and HRP polymer&#44; the reaction was terminated with diaminobenzidine &#40;DAB&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">The GraphPad Prism 9&#46;2&#46;0 software was used for statistical analysis and the generation of graphs&#46; Frequencies between the groups were analyzed using Fisher or Chi-Square tests&#44; and numerical data were analyzed using Kruskal-Wallis tests followed by Dunn&#8217;s multiple comparisons&#46; The result was considered significant when p&#8804;0&#46;05&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Demographic and clinical data &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">There was no statistical difference regarding gender in the three groups&#46; As for age groups&#44; the PF-anti-Dsg3&#40;-&#41; group was younger than the PV group &#40;p&#8239;&#61;&#8239;0&#46;0522&#41;&#46; There was no statistical difference when comparing the PF-anti-Dsg3&#43; with the PF-anti-Dsg3&#40;-&#41; and the PV group &#40;p&#8239;&#61;&#8239;0&#46;5361 and p&#8239;&#62;&#8239;0&#46;9999&#44; respectively&#41;&#46; The generalized form predominated in the PF-anti-Dsg3&#43; group&#44; when compared to the PF-anti-Dsg3&#40;-&#41; group &#40;p&#8239;&#61;&#8239;0&#46;002&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Serological data</span><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding anti-Dsg3 antibodies&#44; the PF-anti-Dsg3&#43; group had lower titers than the PV group &#40;p&#8239;&#60;&#8239;0&#46;0001&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The distribution of anti-Dsg3 titers in the PF-anti-Dsg3&#43; group is depicted in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B shows slight variation over time in anti-Dsg3 titers in six patients&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In the IB performed with sera from 12 patients&#44; three recognized Dsg1&#44; and one recognized Dsg3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; PF10&#44; which recognized Dsg3 in the IB&#44; showed the 2nd highest anti-Dsg3 titer in the ELISA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Expression of Dsgs 1 and 3 with IHC &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">IHC showed internalization of Dsg1&#44; with coarse clumps inside the cytoplasm&#44; sometimes perinuclear&#44; in skin samples from patients in the PF-anti-Dsg3&#40;-&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41; and PF-anti-Dsg3&#43; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#41;&#46; Dsg3 expression occurred in the keratinocyte envelope and intracytoplasmically&#44; with emphasis on its expression throughout the epidermis&#46; No internalization of Dsg3 was observed&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100"><span class="elsevierStyleItalic">HLA-DRB1</span> alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3 &#40;-&#41; groups&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Five &#40;31&#46;3&#37;&#41; of 16 patients in the PF-anti-Dsg3&#43; group&#44; and 16 &#40;38&#46;1&#37;&#41; of 42 in the PF-anti-Dsg3&#40;-&#41; group were typed&#46; In the PF-anti-Dsg3&#43; group&#44; five patients showed one or two susceptibility alleles for PF&#44; and none of them had alleles associated with PV&#46; In the PF-anti-Dsg3&#40;-&#41; group&#44; 11 had alleles of susceptibility to PF&#44; and two patients had alleles of susceptibility to PV in heterozygous form&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The production of serum autoantibodies against Dsg3 is not expected in PF&#44; since&#44; in its pathogenesis&#44; only anti-Dsg1 antibodies are implicated in subgranular acantholysis&#44; with consequent formation of flaccid bullae on the skin&#46; The PF phenotype does not include the mucosal lesions observed in PV due to antibodies against Dsg3&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a> However&#44; autoantibodies against Dsg3 have been rarely reported in PF cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a> More recently&#44; anti-Dsg3 antibodies have been reported in other forms of pemphigus&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Arteaga et al&#46; &#40;2002&#41; described anti-Dsg3 in 7&#37; of 276 patients with PF&#44; demonstrating that anti-Dsg3 antibodies did not show a serological cross-reaction with Dsg1&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Flores et al&#46; &#40;2012&#41; reported anti-Dsg3 in 40&#37; of 101 FS sera&#44; and in 14&#37; of controls from an endemic region for FS in Brazil&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Oliveira et al&#46; &#40;2016&#41; reported anti-Dsg3 in 4&#37; of the patients in a PF series &#40;including patients from the northeastern region of the state of S&#227;o Paulo&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The present series confirmed 6&#46;64&#37; of patients with PF with indeterminate or positive results for anti-Dsg3 in the ELISA test&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">When comparing the three groups&#44; the age range of the PF-anti-Dsg3&#43; group tended to be older&#44; comparable to that of the PV group &#40;p&#62;0&#46;999&#41;&#44; and similar to that of the PF-anti-Dsg3&#40;-&#41; group&#46; The generalized clinical form predominated in the PF-anti-Dsg3&#43; group &#40;p&#61;0&#46;0020&#41;&#46; Regarding the anti-Dsg3 titers of the PF-anti-Dsg3&#43; group&#44; they were lower when compared to those of the PV group &#40;p&#60;0&#46;0001&#41;&#46; The measurement of anti-Dsg3 in the PV group was carried out in treatment-na&#239;ve patients&#44; while in the PF-anti-Dsg3&#43; group&#44; three &#40;20&#37;&#41; of the 15 patients &#40;with information on treatment&#41; were not receiving treatment &#40;PF5&#44; PF6 and PF14&#41;&#46; Anti-Dsg3 titers in the PF-anti-Dsg3&#43; group showed no difference between treated and untreated patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Two patients stand out&#44; in the sample of 16&#44; with higher anti-Dsg3 titers&#44; whose blood was collected while undergoing treatment&#46; Patient PF2&#44; a 63-year-old male&#44; presented the generalized form&#44; with 14 years evolution&#44; and had keratoacanthoma and melanoma during the follow-up&#46; Another patient PF10&#44; 46 years-old male&#44; had the generalized form&#44; and a two-year history&#46; There were coinciding factors in both cases&#44; in addition to higher anti-Dsg3 titers&#44; male gender&#44; having had the onset of PF at an older age&#44; and the generalized form of the disease&#46; IB confirmed the production of anti-Dsg3 only in PF10 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The internalization of Dsgs&#44; in the process of acantholysis&#44; is observed on IHC by the formation of intracytoplasmic and perinuclear granules in keratinocytes&#44; when anti-Dsg1 and 3 antibodies are used in PF and PV&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The internalization of Dsg1 was observed in samples from the PF-anti-Dsg3&#40;-&#41; and PF-anti-Dsg3&#43; groups&#59; however&#44; there was no internalization of Dsg3&#46; The low anti-Dsg3 titers in the PF-anti-Dsg3&#43; group could justify the lack of Dsg3 internalization&#44; as well as the absence of mucosal lesions&#46; In exclusively cutaneous PV&#44; low anti-Dsg3 titers could explain the absence of mucosal lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Although <span class="elsevierStyleItalic">HLA-DRB1</span> alleles were not typed in the whole group of PF-anti-Dsg3&#43;&#44; exclusive alleles of susceptibility to PF were determined in the five individuals that were typed&#44; in homozygous or heterozygous forms&#44; without the presence of alleles associated with PV&#46; Recently&#44; Sielski et al&#46; &#40;2022&#41; demonstrated that cases of PV that contradicted the hypothesis of Dsgs compensation were related to the absence of <span class="elsevierStyleItalic">DRB1</span> alleles of susceptibility to PV&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Therefore&#44; the absence of susceptibility alleles to PV in the PF-anti-Dsg3&#43; group could contribute to the non-pathogenicity of antibodies against Dsg3&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The production of anti-Dsg3 in PF could be justified by the phenomenon of epitope spreading &#8210; patients with a specific bullous disease have non-pathogenic autoantibodies against other molecules of the epidermis that do not cause the specific bullous disease&#46; Its pathogenesis is explained by the exposure of other epidermal molecules during the inflammation process caused by acantholysis&#44; in the case of pemphigus&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#8211;30</span></a> In this study&#44; IHC showed the expression of Dsg3 in all layers of the epidermis&#46; Thus&#44; it could justify the greater exposure of Dsg3&#44; with consequent production of anti-Dsg3&#46; However&#44; this expression in all layers of the epidermis was observed in samples from both groups &#8211; PF-anti-Dsg3&#40;-&#41; and PF-anti-Dsg3&#43;&#46; As the PF-anti-Dsg3&#40;-&#41; group consisted of treatment-na&#239;ve patients&#44; it is not known whether anti-Dsg3 would be produced during pemphigus evolution&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Moreover&#44; there are rare reports of patients with clinically and laboratory-proven PF who migrate to the PV phenotype&#44; or of patients with both PF and PV characteristics&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#8211;34</span></a> However&#44; PV migrating to PF is more commonly observed&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The present case series does not show similar cases&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">The presence of anti-Dsg3 antibodies in PF was related to an older age group &#40;comparable to that of PV&#41; and the generalized form of PF&#46; The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to low anti-Dsg3 titers&#44; the lack of Dsg3 internalization as seen on IHC&#44; and the absence of PV-associated <span class="elsevierStyleItalic">HLA-DRB1</span> alleles&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Financial support</span><p id="par0110" class="elsevierStylePara elsevierViewall">The project was funded by <span class="elsevierStyleGrantSponsor" id="gs0005">FAPESP</span> &#40;Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo&#41; &#40;&#35;2010&#47;51729-2&#41;&#44; SV received a PhD scholarship from <span class="elsevierStyleGrantSponsor" id="gs0010">CAPES</span> &#40;Coordination for the Improvement of Higher Education Personnel&#41; and <span class="elsevierStyleGrantSponsor" id="gs0015">TAJ</span> received a PhD scholarship from FAPESP&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authors&#8217; contributions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Sebastian Vernal&#58; Contributed to data survey&#44; collection and interpretation of data&#59; responsible for blotting assays&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Tamiris Amanda Julio&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for the ELISA assays&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Fernando Henrique Alves&#58; Contributed with data survey and collection of data&#44; and participation in the propaedeutic and therapeutic conduct&#44; and in IB assays&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Aline Turatti&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for DIF&#44; IIF and IHC assays&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Eduardo Antonio Donadi&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for determining <span class="elsevierStyleItalic">HLA-DR</span> alleles&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Ana Maria Roselino&#58; Contributed with the design and planning of the study&#44; collection and analysis of data&#59; drafting and editing of the manuscript&#59; participation in the propaedeutic and&#47;or therapeutic conduct&#59; and critical review of the literature&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">All authors approved the final version of the manuscript&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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              "titulo" => "HLA-DRB1 alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3 &#40;-&#41; groups&#59; Table 2&#41;"
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    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Anti-desmoglein &#40;Dsg&#41;1 is produced in pemphigus foliaceus &#40;PF&#41;&#44; affecting exclusively the skin&#46; Pemphigus vulgaris &#40;PV&#41; shows the production of anti-Dsg3 in the mucosal form&#44; and anti-Dsg1 and 3 in the mucocutaneous form&#46; Anti-Dsg3 autoantibodies have been rarely reported in PF&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparative analytical study of three patients groups&#58; 16 PF-anti-Dsg3&#43;&#44; and 42 PF-anti-Dsg3&#40;-&#41; and 22 PV treatment-na&#239;ve cases&#46; Serum was used in the anti-Dsg1 and 3 ELISA&#44; and in immunoblotting &#40;IB&#41; with human epidermis extract&#46; The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry &#40;IHC&#41;&#46; <span class="elsevierStyleItalic">HLA-DRB1</span> alleles were compiled from a database&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">In the PF-anti-Dsg3&#43; group&#58; age range similar to that of the PV group &#40;p&#8239;&#62;&#8239;0&#46;9999&#41;&#59; predominance of the generalized form of PF &#40;p&#8239;&#61;&#8239;0&#46;002&#41;&#59; anti-Dsg3 titers lower than those of PV &#40;p&#8239;&#60;&#8239;0&#46;0001&#41;&#59; IB confirmed Dsg3 identification in one &#40;8&#46;33&#37;&#41; of 12 patients&#59; IHC showed exclusive cytoplasmic internalization of Dsg1&#59; <span class="elsevierStyleItalic">HLA-DRB1</span> alleles of susceptibility to PF&#44; with the absence of alleles associated with PV&#44; in the five typed patients&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Most of the patients in the PF-anti-Dsg3&#43; group were undergoing treatment&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The presence of anti-Dsg3 antibodies in PF was related to older age &#40;comparable to that of PV&#41; and the generalized form of PF&#46; The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers&#44; the lack of Dsg3 internalization as detected by IHC&#44; and the absence of PV-associated <span class="elsevierStyleItalic">HLA-DRB1</span> alleles&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
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            "identificador" => "abst0025"
            "titulo" => "Study limitations"
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          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclusion"
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Laboratory of the Dermatology Division&#44; Hospital das Cl&#237;nicas&#44; Faculty of Medicine of Ribeir&#227;o Preto&#44; Universidade de S&#227;o Paulo&#44; S&#227;o Paulo&#44; SP&#44; Brazil&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1103
            "Ancho" => 2508
            "Tamanyo" => 197691
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Anti-Dsg1 and anti-Dsg3 titration by ELISA in the PF-anti-Dsg3&#43; group&#46;</span> Values &#8805; 20&#8239;U&#47;mL&#44; between 9&#8210;20&#8239;U&#47;mL and &#60; 9&#8239;U&#47;mL were considered positive&#44; indeterminate and negative&#44; respectively &#40;MBL&#44; Jp&#41;&#46; &#40;A&#41; Serum titration of the 16 patients in the first appointment&#46; Patients PF5 and PF14&#58; serum was collected while treatment-na&#239;ve&#59; PF6&#44; without treatment for more than 60 days&#59; PF3&#44; treatment not included&#59; the others were undergoing treatment&#46; Patients PF4&#44; PF5 and PF7&#58; localized clinical form&#44; the others&#44; generalized form&#46; The &#43; and &#43;&#43; symbols above the bars indicate serum positivity in the IB &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; &#40;B&#41; Serial titration of six patients&#46; The line above the graph shows the number of patients&#46; Each symbol corresponds to a serum sample collected on consecutive dates&#59; the vertical lines show the variation in titles &#40;minimum and maximum&#41;&#59; and the horizontal line&#44; the median&#46; Observe the slight variation in anti-Dsg3 titers&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 852
            "Ancho" => 3008
            "Tamanyo" => 191556
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Immunoblotting with serum samples from 12 patients in the PF-anti-Dsg3&#43; group &#40;some with consecutive samples&#41; and protein extract from human epidermis&#46;</span> Positive controls correspond to samples of pemphigus foliaceus &#40;PF&#41;&#44; which recognize Dsg1 &#40;160&#8239;kDa&#41;&#44; and pemphigus vulgaris &#40;PV&#41;&#44; which recognizes Dsg1 and 3 &#40;130&#8239;kDa&#41;&#46; Negative controls correspond to samples from healthy individuals&#46; Observe the nitrocellulose strips with the 160&#8239;kDa band &#40;&#42;&#41; corresponding to patients PF2&#44; PF12 and PF16&#44; and the 130&#8239;kDa band &#40;&#42;&#42;&#41; corresponding to PF10&#46; For ELISA titers of anti-Dsg1 and anti-Dsg 3 see<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 3983
            "Ancho" => 2675
            "Tamanyo" => 1976854
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">IHC images with Dsg1 and Dsg3 expression stained with DAB in paraffin sections from bullous lesion biopsies showing superficial acantholysis&#46;</span> &#40;A&#41; Control sample from the PF-anti-Dsg3&#40;-&#41; group&#46; Observe Dsg1 expression in intracytoplasmic clumps&#44; and Dsg3 expression throughout the epidermis&#46; &#40;B&#41; Sample from patient PF8 in the anti-Dsg3&#43; group&#46; The Dsg1 and Dsg3 expressions are similar to those of the PF control&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
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          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#35;</span>Series&#58; n&#8239;&#61;&#8239;16&#44; n&#8239;&#61;&#8239;39 and n&#8239;&#61;&#8239;21&#44; respectively&#59; cut-off level for positivity &#8805; 20&#8239;U&#47;mL&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">U&#44; Unavailable&#59; NA&#44; Not Applicable&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">PF-anti-Dsg3&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">PF-anti-Dsg3&#40;-&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">PV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Gender</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;296</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median &#40;minimum&#8210;maximum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;5 &#40;12&#8210;74&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;12&#8210;71&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;13&#8210;72&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;5361&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#62;0&#46;9999&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>0&#46;0522&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Clinical form</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Localized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">U&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Treatment</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment-na&#239;ve&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No treatment &#62;60 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Undergoing treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">U&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Anti-Dsg1 &#40;UR&#47;L&#41;<span class="elsevierStyleSup">&#35;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median &#40;25&#37;&#8210;75&#37; quartiles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">189&#46;0 &#40;135&#46;1&#8210;254&#46;5&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166&#46;9 &#40;121&#46;7&#8210;203&#46;7&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;94 &#40;3&#46;3&#8210;99&#46;4&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;4515&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Anti-Dsg3 &#40;UR&#47;L&#41;<span class="elsevierStyleSup">&#35;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median &#40;25&#37;&#8210;75&#37; quartiles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;1 &#40;23&#46;2&#8210;63&#46;0&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;688 &#40;0&#46;3&#8210;1&#46;6&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">128&#46;6 &#40;56&#46;6&#8210;168&#46;6&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;0002&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; clinical and antibody against Dsg1 and 3 data of the PF-anti-Dsg3&#43; group&#44; compared to the PF-anti-Dsg3&#40;-&#41; and PV groups&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#35;</span>Patients with higher anti-Dsg3 titers &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; In orange and yellow&#58; susceptibility alleles to PF in the northeastern region of the state of S&#227;o Paulo and in other regions of Brazil&#44; respectively&#46; In dark green&#58; PF resistance allele described in other regions of Brazil&#46; In red and light green&#58; susceptibility and resistance alleles to PV&#44; respectively&#44; in the northeastern region of the state of S&#227;o Paulo&#46; PF and PV association alleles were collected from Franco Brochado et al&#46;&#44; 2016<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> and Franco Brochado et al&#46;&#44; 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Distribution of <span class="elsevierStyleItalic">HLA-DRB1</span> alleles associated with pemphigus foliaceus &#40;PF&#41; and pemphigus vulgaris &#40;PV&#41; in the groups PF-anti-Dsg3&#43; and PF-antiDsg3&#40;-&#41;&#46;</p>"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Classification and antigen molecules of autoimmune bullous diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Hashimoto"
                            1 => "H&#46; Qian"
                            2 => "N&#46; Ishii"
                            3 => "T&#46; Nakama"
                            4 => "C&#46; Tateishi"
                            5 => "D&#46; Tsuruta"
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                    0 => array:2 [
                      "doi" => "10.3390/biom13040703"
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                        "tituloSerie" => "Biomolecules"
                        "fecha" => "2023"
                        "volumen" => "13"
                        "paginaInicial" => "703"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37189450"
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            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoimmune bullous skin diseases&#44; pemphigus and pemphigoid"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Egami"
                            1 => "J&#46; Yamagami"
                            2 => "M&#46; Amagai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2020.02.013"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2020"
                        "volumen" => "145"
                        "paginaInicial" => "1031"
                        "paginaFinal" => "1047"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32272980"
                            "web" => "Medline"
                          ]
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            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pemphigus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Schmidt"
                            1 => "M&#46; Kasperkiewicz"
                            2 => "P&#46; Joly"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(19)31778-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2019"
                        "volumen" => "394"
                        "paginaInicial" => "882"
                        "paginaFinal" => "884"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31498102"
                            "web" => "Medline"
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              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Spatial distribution of pemphigus occurrence over five decades in southeastern Brazil"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;S&#46; Celere"
                            1 => "S&#46; Vernal"
                            2 => "L&#46; La Serra"
                            3 => "M&#46;J&#46; Franco Brochado"
                            4 => "L&#46;E&#46; Moschini"
                            5 => "A&#46;M&#46; Roselino"
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                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4269/ajtmh.17-0100"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Trop Med Hyg"
                        "fecha" => "2017"
                        "volumen" => "97"
                        "paginaInicial" => "1737"
                        "paginaFinal" => "1745"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29016334"
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              "etiqueta" => "5"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Geographical foci and epidemiological changes of pemphigus vulgaris in four decades in Southeastern Brazil"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46;S&#46; Celere"
                            1 => "S&#46; Vernal"
                            2 => "M&#46;J&#46;F&#46; Brochado"
                            3 => "S&#46;I&#46; Segura-Mu&#241;oz"
                            4 => "A&#46;M&#46; Roselino"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Dermatol"
                        "fecha" => "2017"
                        "volumen" => "56"
                        "paginaInicial" => "1494"
                        "paginaFinal" => "1496"
                      ]
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              "etiqueta" => "6"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The human genes for desmogleins &#40;DSG1 and DSG3&#41; are located in a small region on chromosome 18q12"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Wang"
                            1 => "M&#46; Amagai"
                            2 => "S&#46; Minoshima"
                            3 => "K&#46; Sakai"
                            4 => "K&#46;J&#46; Green"
                            5 => "T&#46; Nishikawa"
                          ]
                        ]
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Original Article
Factors associated with non-pathogenic antibodies against desmoglein-3 in pemphigus foliaceus
Sebastian Vernala, Tamiris Amanda Juliob, Fernando Henrique Alvesb, Aline Turattia, Eduardo Antonio Donadic, Ana Maria Roselinoa,b,
Corresponding author
amfrosel@fmrp.usp.br

Corresponding author.
a Laboratory of the Dermatology Division, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, SP, Brazil
b Division of Dermatology, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, SP, Brazil
c Division of Immunology, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, SP, Brazil
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in Brazil&#41; affects exclusively the skin of young adults&#44; with anti-Dsg1 production&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Dsg1 and 3 are transmembrane proteins of 160kDa and 130kDa&#44; respectively&#44; expressed by genes located on chromosome 18&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Dsgs compensation theory explains the level of intraepidermal acantholysis in pemphigus&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Anti-Dsg1 antibodies in PF cause subgranular acantholysis&#44; as Dsg1 is expressed more intensily in the upper layers of the epidermis&#46; Anti-Dsg3 antibodies cause suprabasal acantholysis&#44; as Dsg3 is most often expressed in the lower layers of the epidermis&#44; and in all epithelial layers in the mucous membranes&#46; Moreover&#44; as there is a lower expression of Dsg1 in the mucosa&#44; it is not affected by anti-Dsg1 antibodies in PF&#44; as Dsg3 compensates for epithelial cell cohesion in the mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Subsequently&#44; the hypothesis of Dsgs compensation&#44; to explain the level of cleavage of epidermal acantholysis related to the production of anti-Dsg1 and 3&#44; started to be discussed again&#44; since exclusively suprabasal acantholysis in PV would not be explained in the mucocutaneous form&#44; when anti-Dsg1 is also present&#46; Other target molecules of epidermal adhesion are now identified in the pathogenesis of pemphigus&#44; as well as mitochondrial proteins&#44; cholinergic receptors&#44; and other molecules&#44; which act synergistically with anti-Dsg1 and Dsg3 antibodies in epidermal acantholysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;18</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">As both PV and PF are prevalent in southeastern Brazil&#44; there is an opportunity for outpatient follow-up of a large series of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> In the PF series&#44; over a 25-year period&#44; it was observed that 6&#44;64 &#37; of the patients&#44; in addition to being positive for anti-Dsg1&#44; also had reactive titers to Dsg3 in the ELISA test&#44; without&#44; however&#44; showing a phenotype of mucosal lesions&#46; Therefore&#44; we aimed to analyze clinical-laboratory data in the group of patients with PF and reactivity to Dsg3 &#40;PF-anti-Dsg3&#43;&#41;&#46; For this purpose&#44; three groups were compared&#58; PF-anti-Dsg3&#43;&#44; PF with anti-Dsg3 negativity and treatment-na&#239;ve &#91;PF-anti-Dsg3&#40;&#727;&#41;&#93;&#44; and treatment-na&#239;ve PV&#46; For specific purposes&#44; the following were evaluated&#58; &#40;i&#41; Demographic and clinical data&#59; &#40;ii&#41; Temporal evolution of anti-Dsg1 and 3 titers by ELISA and identification of Dsg1 and 3 by immunoblotting &#40;IB&#41; in the PF-anti-Dsg3&#43; group&#59; and &#40;iii&#41; Expression of Dsg1 and 3 in paraffin-embedded skin biopsies by immunohistochemistry &#40;IHC&#41; and &#40;iv&#41; typification of <span class="elsevierStyleItalic">HLA-DRB1</span> alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3&#40;-&#41; groups&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is a comparative analytical study of three groups&#46; The sample bank of the Dermatology Laboratory&#44; Hospital das Cl&#237;nicas&#44; FMRP-USP&#44; has the approval of the Research Ethics Committee &#40;HCRP Process number 3605&#47;2006&#41;&#46; Patients and control individuals signed the free and informed consent form at the time of sample collection&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Case series</span><p id="par0025" class="elsevierStylePara elsevierViewall">It consisted of 80 patients&#58; 16 PF-anti-Dsg3&#43;&#44; 42 PF-anti-Dsg3&#40;-&#41; and 22 PV cases&#46; The clinical findings were confirmed by histopathological examination and by direct immunofluorescence &#40;DIF&#41; and&#47;or indirect immunofluorescence &#40;IIF&#41;&#46; Demographic&#44; clinical and laboratory data &#40;anti-Dsg1 and Dsg3 by ELISA and HLA alleles&#41; were obtained from data recorded at the Laboratory of Dermatology&#46; In the PF-anti-Dsg3&#43; group&#44; three &#40;20&#37;&#41; of the 15 patients &#40;with information about treatment&#41; were untreated at the time of blood collection&#44; while 42 of the PF-anti-Dsg3&#40;-&#41; patients and 22&#8239;PV were all treatment-na&#239;ve&#46; Immunoblotting &#40;IB&#41; assays were performed with 12 &#40;75&#37;&#41; of the 16 serum samples from the PF-anti-Dsg3&#43; group&#44; with some patients having more than one sample analyzed&#44; collected at different times&#46; IHC was performed on sections from the paraffin blocks of four patients from the PF-anti-Dsg3&#43; group and one from the PF-anti-Dsg3&#40;-&#41; group&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">ELISA for the detection of IgG antibodies against Dsg1 and 3</span><p id="par0030" class="elsevierStylePara elsevierViewall">The manufacturers recommendations were followed&#46; Values &#8805; 20&#8239;U&#47;mL&#44; between 9&#8210;20&#8239;U&#47;mL and &#60; 9&#8239;U&#47;mL were considered positive&#44; indeterminate and negative&#44; respectively &#40;MBL&#44; Nagoya&#44; Japan&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">IB with human epidermis extract and patient serum</span><p id="par0035" class="elsevierStylePara elsevierViewall">Briefly&#44; skin fragments were incubated for 48&#8239;h in PBS with EDTA &#40;Merck&#41; and PMSF &#40;Sigma-Aldrich&#41; to separate the epidermis from the dermis&#46; Protein extraction from the epidermis was carried out with a Tris-HCL&#44; SDS&#44; 2-mercaptoethanol solution&#44; and then an EDTA&#44; PMSF and proteinase inhibitor cocktail &#40;Sigma-Aldrich&#41; were added&#46; After the electrophoretic run&#44; the polyacrylamide gel was assembled in a sandwich with a 0&#46;45&#8239;&#181;m nitrocellulose membrane &#40;BioRad&#41; for protein transfer&#46; After blocking with 3&#37; skimmed milk in TBS&#44; and consecutive washings&#44; the serum samples &#40;1&#58;20&#41; were incubated on nitrocellulose strips&#44; followed by incubation with anti-human HRP IgG secondary antibody &#40;BioRad&#41;&#46; After washing&#44; color reagent &#40;Color-Plus HRP&#44; BioRad&#41; was added for colorimetric development&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Expression of Dsgs1 and 3 in paraffin-embedded samples with IHC</span><p id="par0040" class="elsevierStylePara elsevierViewall">For IHC assays&#44; the manufacturers recommendations were followed &#40;HRP-Polymer MACH1&#44; Biocare Medical&#44; Concord&#44; CA&#44; USA&#41;&#46; Briefly&#44; 5&#956;m sections were obtained and after antigen retrieval in citrate&#44; inhibition of endogenous peroxidase and use of a blocking solution&#44; were incubated with anti-Dsg1 and 3 monoclonal antibodies produced in mice &#40;Abcam&#44; MA&#44; USA&#41;&#46; After washing and incubation with Probe and HRP polymer&#44; the reaction was terminated with diaminobenzidine &#40;DAB&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">The GraphPad Prism 9&#46;2&#46;0 software was used for statistical analysis and the generation of graphs&#46; Frequencies between the groups were analyzed using Fisher or Chi-Square tests&#44; and numerical data were analyzed using Kruskal-Wallis tests followed by Dunn&#8217;s multiple comparisons&#46; The result was considered significant when p&#8804;0&#46;05&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Demographic and clinical data &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">There was no statistical difference regarding gender in the three groups&#46; As for age groups&#44; the PF-anti-Dsg3&#40;-&#41; group was younger than the PV group &#40;p&#8239;&#61;&#8239;0&#46;0522&#41;&#46; There was no statistical difference when comparing the PF-anti-Dsg3&#43; with the PF-anti-Dsg3&#40;-&#41; and the PV group &#40;p&#8239;&#61;&#8239;0&#46;5361 and p&#8239;&#62;&#8239;0&#46;9999&#44; respectively&#41;&#46; The generalized form predominated in the PF-anti-Dsg3&#43; group&#44; when compared to the PF-anti-Dsg3&#40;-&#41; group &#40;p&#8239;&#61;&#8239;0&#46;002&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Serological data</span><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding anti-Dsg3 antibodies&#44; the PF-anti-Dsg3&#43; group had lower titers than the PV group &#40;p&#8239;&#60;&#8239;0&#46;0001&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The distribution of anti-Dsg3 titers in the PF-anti-Dsg3&#43; group is depicted in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B shows slight variation over time in anti-Dsg3 titers in six patients&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In the IB performed with sera from 12 patients&#44; three recognized Dsg1&#44; and one recognized Dsg3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; PF10&#44; which recognized Dsg3 in the IB&#44; showed the 2nd highest anti-Dsg3 titer in the ELISA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Expression of Dsgs 1 and 3 with IHC &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">IHC showed internalization of Dsg1&#44; with coarse clumps inside the cytoplasm&#44; sometimes perinuclear&#44; in skin samples from patients in the PF-anti-Dsg3&#40;-&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41; and PF-anti-Dsg3&#43; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#41;&#46; Dsg3 expression occurred in the keratinocyte envelope and intracytoplasmically&#44; with emphasis on its expression throughout the epidermis&#46; No internalization of Dsg3 was observed&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100"><span class="elsevierStyleItalic">HLA-DRB1</span> alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3 &#40;-&#41; groups&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Five &#40;31&#46;3&#37;&#41; of 16 patients in the PF-anti-Dsg3&#43; group&#44; and 16 &#40;38&#46;1&#37;&#41; of 42 in the PF-anti-Dsg3&#40;-&#41; group were typed&#46; In the PF-anti-Dsg3&#43; group&#44; five patients showed one or two susceptibility alleles for PF&#44; and none of them had alleles associated with PV&#46; In the PF-anti-Dsg3&#40;-&#41; group&#44; 11 had alleles of susceptibility to PF&#44; and two patients had alleles of susceptibility to PV in heterozygous form&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The production of serum autoantibodies against Dsg3 is not expected in PF&#44; since&#44; in its pathogenesis&#44; only anti-Dsg1 antibodies are implicated in subgranular acantholysis&#44; with consequent formation of flaccid bullae on the skin&#46; The PF phenotype does not include the mucosal lesions observed in PV due to antibodies against Dsg3&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a> However&#44; autoantibodies against Dsg3 have been rarely reported in PF cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a> More recently&#44; anti-Dsg3 antibodies have been reported in other forms of pemphigus&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Arteaga et al&#46; &#40;2002&#41; described anti-Dsg3 in 7&#37; of 276 patients with PF&#44; demonstrating that anti-Dsg3 antibodies did not show a serological cross-reaction with Dsg1&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Flores et al&#46; &#40;2012&#41; reported anti-Dsg3 in 40&#37; of 101 FS sera&#44; and in 14&#37; of controls from an endemic region for FS in Brazil&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Oliveira et al&#46; &#40;2016&#41; reported anti-Dsg3 in 4&#37; of the patients in a PF series &#40;including patients from the northeastern region of the state of S&#227;o Paulo&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The present series confirmed 6&#46;64&#37; of patients with PF with indeterminate or positive results for anti-Dsg3 in the ELISA test&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">When comparing the three groups&#44; the age range of the PF-anti-Dsg3&#43; group tended to be older&#44; comparable to that of the PV group &#40;p&#62;0&#46;999&#41;&#44; and similar to that of the PF-anti-Dsg3&#40;-&#41; group&#46; The generalized clinical form predominated in the PF-anti-Dsg3&#43; group &#40;p&#61;0&#46;0020&#41;&#46; Regarding the anti-Dsg3 titers of the PF-anti-Dsg3&#43; group&#44; they were lower when compared to those of the PV group &#40;p&#60;0&#46;0001&#41;&#46; The measurement of anti-Dsg3 in the PV group was carried out in treatment-na&#239;ve patients&#44; while in the PF-anti-Dsg3&#43; group&#44; three &#40;20&#37;&#41; of the 15 patients &#40;with information on treatment&#41; were not receiving treatment &#40;PF5&#44; PF6 and PF14&#41;&#46; Anti-Dsg3 titers in the PF-anti-Dsg3&#43; group showed no difference between treated and untreated patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Two patients stand out&#44; in the sample of 16&#44; with higher anti-Dsg3 titers&#44; whose blood was collected while undergoing treatment&#46; Patient PF2&#44; a 63-year-old male&#44; presented the generalized form&#44; with 14 years evolution&#44; and had keratoacanthoma and melanoma during the follow-up&#46; Another patient PF10&#44; 46 years-old male&#44; had the generalized form&#44; and a two-year history&#46; There were coinciding factors in both cases&#44; in addition to higher anti-Dsg3 titers&#44; male gender&#44; having had the onset of PF at an older age&#44; and the generalized form of the disease&#46; IB confirmed the production of anti-Dsg3 only in PF10 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The internalization of Dsgs&#44; in the process of acantholysis&#44; is observed on IHC by the formation of intracytoplasmic and perinuclear granules in keratinocytes&#44; when anti-Dsg1 and 3 antibodies are used in PF and PV&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The internalization of Dsg1 was observed in samples from the PF-anti-Dsg3&#40;-&#41; and PF-anti-Dsg3&#43; groups&#59; however&#44; there was no internalization of Dsg3&#46; The low anti-Dsg3 titers in the PF-anti-Dsg3&#43; group could justify the lack of Dsg3 internalization&#44; as well as the absence of mucosal lesions&#46; In exclusively cutaneous PV&#44; low anti-Dsg3 titers could explain the absence of mucosal lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Although <span class="elsevierStyleItalic">HLA-DRB1</span> alleles were not typed in the whole group of PF-anti-Dsg3&#43;&#44; exclusive alleles of susceptibility to PF were determined in the five individuals that were typed&#44; in homozygous or heterozygous forms&#44; without the presence of alleles associated with PV&#46; Recently&#44; Sielski et al&#46; &#40;2022&#41; demonstrated that cases of PV that contradicted the hypothesis of Dsgs compensation were related to the absence of <span class="elsevierStyleItalic">DRB1</span> alleles of susceptibility to PV&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Therefore&#44; the absence of susceptibility alleles to PV in the PF-anti-Dsg3&#43; group could contribute to the non-pathogenicity of antibodies against Dsg3&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The production of anti-Dsg3 in PF could be justified by the phenomenon of epitope spreading &#8210; patients with a specific bullous disease have non-pathogenic autoantibodies against other molecules of the epidermis that do not cause the specific bullous disease&#46; Its pathogenesis is explained by the exposure of other epidermal molecules during the inflammation process caused by acantholysis&#44; in the case of pemphigus&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#8211;30</span></a> In this study&#44; IHC showed the expression of Dsg3 in all layers of the epidermis&#46; Thus&#44; it could justify the greater exposure of Dsg3&#44; with consequent production of anti-Dsg3&#46; However&#44; this expression in all layers of the epidermis was observed in samples from both groups &#8211; PF-anti-Dsg3&#40;-&#41; and PF-anti-Dsg3&#43;&#46; As the PF-anti-Dsg3&#40;-&#41; group consisted of treatment-na&#239;ve patients&#44; it is not known whether anti-Dsg3 would be produced during pemphigus evolution&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Moreover&#44; there are rare reports of patients with clinically and laboratory-proven PF who migrate to the PV phenotype&#44; or of patients with both PF and PV characteristics&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#8211;34</span></a> However&#44; PV migrating to PF is more commonly observed&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The present case series does not show similar cases&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">The presence of anti-Dsg3 antibodies in PF was related to an older age group &#40;comparable to that of PV&#41; and the generalized form of PF&#46; The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to low anti-Dsg3 titers&#44; the lack of Dsg3 internalization as seen on IHC&#44; and the absence of PV-associated <span class="elsevierStyleItalic">HLA-DRB1</span> alleles&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Financial support</span><p id="par0110" class="elsevierStylePara elsevierViewall">The project was funded by <span class="elsevierStyleGrantSponsor" id="gs0005">FAPESP</span> &#40;Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo&#41; &#40;&#35;2010&#47;51729-2&#41;&#44; SV received a PhD scholarship from <span class="elsevierStyleGrantSponsor" id="gs0010">CAPES</span> &#40;Coordination for the Improvement of Higher Education Personnel&#41; and <span class="elsevierStyleGrantSponsor" id="gs0015">TAJ</span> received a PhD scholarship from FAPESP&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authors&#8217; contributions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Sebastian Vernal&#58; Contributed to data survey&#44; collection and interpretation of data&#59; responsible for blotting assays&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Tamiris Amanda Julio&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for the ELISA assays&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Fernando Henrique Alves&#58; Contributed with data survey and collection of data&#44; and participation in the propaedeutic and therapeutic conduct&#44; and in IB assays&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Aline Turatti&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for DIF&#44; IIF and IHC assays&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Eduardo Antonio Donadi&#58; Contributed with data survey&#44; collection and interpretation of data&#59; responsible for determining <span class="elsevierStyleItalic">HLA-DR</span> alleles&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Ana Maria Roselino&#58; Contributed with the design and planning of the study&#44; collection and analysis of data&#59; drafting and editing of the manuscript&#59; participation in the propaedeutic and&#47;or therapeutic conduct&#59; and critical review of the literature&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">All authors approved the final version of the manuscript&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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              "titulo" => "HLA-DRB1 alleles associated with PF and PV in the PF-anti-Dsg3&#43; and PF-anti-Dsg3 &#40;-&#41; groups&#59; Table 2&#41;"
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            0 => "Desmoglein 1"
            1 => "Desmoglein 2"
            2 => "Desmoglein 3"
            3 => "Endemic Pemphigus Foliaceus"
            4 => "HLA-DRB1 Chains"
            5 => "Pemphigus"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Anti-desmoglein &#40;Dsg&#41;1 is produced in pemphigus foliaceus &#40;PF&#41;&#44; affecting exclusively the skin&#46; Pemphigus vulgaris &#40;PV&#41; shows the production of anti-Dsg3 in the mucosal form&#44; and anti-Dsg1 and 3 in the mucocutaneous form&#46; Anti-Dsg3 autoantibodies have been rarely reported in PF&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparative analytical study of three patients groups&#58; 16 PF-anti-Dsg3&#43;&#44; and 42 PF-anti-Dsg3&#40;-&#41; and 22 PV treatment-na&#239;ve cases&#46; Serum was used in the anti-Dsg1 and 3 ELISA&#44; and in immunoblotting &#40;IB&#41; with human epidermis extract&#46; The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry &#40;IHC&#41;&#46; <span class="elsevierStyleItalic">HLA-DRB1</span> alleles were compiled from a database&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">In the PF-anti-Dsg3&#43; group&#58; age range similar to that of the PV group &#40;p&#8239;&#62;&#8239;0&#46;9999&#41;&#59; predominance of the generalized form of PF &#40;p&#8239;&#61;&#8239;0&#46;002&#41;&#59; anti-Dsg3 titers lower than those of PV &#40;p&#8239;&#60;&#8239;0&#46;0001&#41;&#59; IB confirmed Dsg3 identification in one &#40;8&#46;33&#37;&#41; of 12 patients&#59; IHC showed exclusive cytoplasmic internalization of Dsg1&#59; <span class="elsevierStyleItalic">HLA-DRB1</span> alleles of susceptibility to PF&#44; with the absence of alleles associated with PV&#44; in the five typed patients&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Most of the patients in the PF-anti-Dsg3&#43; group were undergoing treatment&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The presence of anti-Dsg3 antibodies in PF was related to older age &#40;comparable to that of PV&#41; and the generalized form of PF&#46; The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers&#44; the lack of Dsg3 internalization as detected by IHC&#44; and the absence of PV-associated <span class="elsevierStyleItalic">HLA-DRB1</span> alleles&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Laboratory of the Dermatology Division&#44; Hospital das Cl&#237;nicas&#44; Faculty of Medicine of Ribeir&#227;o Preto&#44; Universidade de S&#227;o Paulo&#44; S&#227;o Paulo&#44; SP&#44; Brazil&#46;</p>"
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          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1103
            "Ancho" => 2508
            "Tamanyo" => 197691
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Anti-Dsg1 and anti-Dsg3 titration by ELISA in the PF-anti-Dsg3&#43; group&#46;</span> Values &#8805; 20&#8239;U&#47;mL&#44; between 9&#8210;20&#8239;U&#47;mL and &#60; 9&#8239;U&#47;mL were considered positive&#44; indeterminate and negative&#44; respectively &#40;MBL&#44; Jp&#41;&#46; &#40;A&#41; Serum titration of the 16 patients in the first appointment&#46; Patients PF5 and PF14&#58; serum was collected while treatment-na&#239;ve&#59; PF6&#44; without treatment for more than 60 days&#59; PF3&#44; treatment not included&#59; the others were undergoing treatment&#46; Patients PF4&#44; PF5 and PF7&#58; localized clinical form&#44; the others&#44; generalized form&#46; The &#43; and &#43;&#43; symbols above the bars indicate serum positivity in the IB &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; &#40;B&#41; Serial titration of six patients&#46; The line above the graph shows the number of patients&#46; Each symbol corresponds to a serum sample collected on consecutive dates&#59; the vertical lines show the variation in titles &#40;minimum and maximum&#41;&#59; and the horizontal line&#44; the median&#46; Observe the slight variation in anti-Dsg3 titers&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 852
            "Ancho" => 3008
            "Tamanyo" => 191556
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Immunoblotting with serum samples from 12 patients in the PF-anti-Dsg3&#43; group &#40;some with consecutive samples&#41; and protein extract from human epidermis&#46;</span> Positive controls correspond to samples of pemphigus foliaceus &#40;PF&#41;&#44; which recognize Dsg1 &#40;160&#8239;kDa&#41;&#44; and pemphigus vulgaris &#40;PV&#41;&#44; which recognizes Dsg1 and 3 &#40;130&#8239;kDa&#41;&#46; Negative controls correspond to samples from healthy individuals&#46; Observe the nitrocellulose strips with the 160&#8239;kDa band &#40;&#42;&#41; corresponding to patients PF2&#44; PF12 and PF16&#44; and the 130&#8239;kDa band &#40;&#42;&#42;&#41; corresponding to PF10&#46; For ELISA titers of anti-Dsg1 and anti-Dsg 3 see<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 3983
            "Ancho" => 2675
            "Tamanyo" => 1976854
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Figure "
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">IHC images with Dsg1 and Dsg3 expression stained with DAB in paraffin sections from bullous lesion biopsies showing superficial acantholysis&#46;</span> &#40;A&#41; Control sample from the PF-anti-Dsg3&#40;-&#41; group&#46; Observe Dsg1 expression in intracytoplasmic clumps&#44; and Dsg3 expression throughout the epidermis&#46; &#40;B&#41; Sample from patient PF8 in the anti-Dsg3&#43; group&#46; The Dsg1 and Dsg3 expressions are similar to those of the PF control&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#35;</span>Series&#58; n&#8239;&#61;&#8239;16&#44; n&#8239;&#61;&#8239;39 and n&#8239;&#61;&#8239;21&#44; respectively&#59; cut-off level for positivity &#8805; 20&#8239;U&#47;mL&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">U&#44; Unavailable&#59; NA&#44; Not Applicable&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">PF-anti-Dsg3&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">PF-anti-Dsg3&#40;-&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">PV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#8239;&#61;&#8239;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Gender</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;296</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Median &#40;minimum&#8210;maximum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;5 &#40;12&#8210;74&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;12&#8210;71&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;13&#8210;72&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;5361&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#62;0&#46;9999&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>0&#46;0522&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Clinical form</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Localized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalized&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">U&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Treatment</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment-na&#239;ve&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No treatment &#62;60 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Undergoing treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">U&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;4515&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Anti-Dsg3 &#40;UR&#47;L&#41;<span class="elsevierStyleSup">&#35;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">33&#46;1 &#40;23&#46;2&#8210;63&#46;0&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;688 &#40;0&#46;3&#8210;1&#46;6&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">128&#46;6 &#40;56&#46;6&#8210;168&#46;6&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">b</span>0&#46;0002&#59; <span class="elsevierStyleSup">a</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&#59; <span class="elsevierStyleSup">b</span>&#183;<span class="elsevierStyleSup">c</span>&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Classification and antigen molecules of autoimmune bullous diseases"
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                          "autores" => array:6 [
                            0 => "T&#46; Hashimoto"
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                            2 => "N&#46; Ishii"
                            3 => "T&#46; Nakama"
                            4 => "C&#46; Tateishi"
                            5 => "D&#46; Tsuruta"
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                        "volumen" => "13"
                        "paginaInicial" => "703"
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                    0 => array:2 [
                      "titulo" => "Autoimmune bullous skin diseases&#44; pemphigus and pemphigoid"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Egami"
                            1 => "J&#46; Yamagami"
                            2 => "M&#46; Amagai"
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                      ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2020.02.013"
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                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2020"
                        "volumen" => "145"
                        "paginaInicial" => "1031"
                        "paginaFinal" => "1047"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32272980"
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                      "titulo" => "Pemphigus"
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                          "autores" => array:3 [
                            0 => "E&#46; Schmidt"
                            1 => "M&#46; Kasperkiewicz"
                            2 => "P&#46; Joly"
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                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(19)31778-7"
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2019"
                        "volumen" => "394"
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                        "paginaFinal" => "884"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31498102"
                            "web" => "Medline"
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                            3 => "M&#46;J&#46; Franco Brochado"
                            4 => "L&#46;E&#46; Moschini"
                            5 => "A&#46;M&#46; Roselino"
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                        "tituloSerie" => "Am J Trop Med Hyg"
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