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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">Dentre os crit&#233;rios listados tanto pelo <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#8208;82&#41; quanto pelo <span class="elsevierStyleItalic">Systemic Lupus International Collaborating Clinics</span> &#40;SLICC&#8208;12&#41; para o diagn&#243;stico de l&#250;pus eritematoso sist&#234;mico &#40;LES&#41;&#44; quatro est&#227;o relacionados a altera&#231;&#245;es na pele e mucosas&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;2</span></a> L&#250;pus eritematoso cut&#226;neo &#40;LEC&#41; &#233; um dos achados mais evidentes&#44; mas apenas uma fra&#231;&#227;o dos pacientes com LEC ir&#225; eventualmente desenvolver LES&#58; entre os pacientes com l&#250;pus eritematoso discoide &#40;LED&#41;&#44; o subtipo mais comum de LEC&#44; a frequ&#234;ncia de progress&#227;o para LES varia de 0&#37; a 28&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> As caracter&#237;sticas que levam o m&#233;dico a suspeitar que isso possa acontecer incluem o n&#250;mero e a gravidade das les&#245;es cut&#226;neas&#44; o t&#237;tulo de anticorpos antinucleares e a presen&#231;a de sintomas sist&#234;micos no in&#237;cio da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> A possibilidade de progress&#227;o para LES causa ansiedade em pacientes com l&#250;pus cut&#226;neo&#46; &#201; importante&#44; ent&#227;o&#44; tentar determinar quais pacientes t&#234;m maior risco de progress&#227;o para doen&#231;a sist&#234;mica&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Pesquisas anteriores mostraram a import&#226;ncia das vias pr&#243;&#8208;inflamat&#243;rias e citot&#243;xicas na g&#234;nese do l&#250;pus eritematoso&#44; geralmente comparando os subtipos de LEC&#46; Entretanto&#44; poucos estudos t&#234;m se concentrado nas diferen&#231;as entre pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e aqueles LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#46; O objetivo do presente estudo foi encontrar biomarcadores inflamat&#243;rios que pudessem predizer a progress&#227;o do LEC para LES&#46; Com esse prop&#243;sito&#44; foram utilizados ensaios imuno&#8208;histoqu&#237;micos &#40;IHQ&#41; em biopsias de pele de pacientes com LEC &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 1</a>&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Biopsias de pele de 59 pacientes com LEC atendidos no Ambulat&#243;rio de Dermatologia entre 1995 e 2012 foram inclu&#237;das se&#58; 1&#41; registros m&#233;dicos completos estivessem dispon&#237;veis&#59; 2&#41; o diagn&#243;stico tivesse sido confirmado por exame cl&#237;nico e histopatol&#243;gico&#44; incluindo imunofluoresc&#234;ncia direta&#44; quando indicada&#59; e 3&#41; houvesse tecido suficiente no bloco de parafina para novos cortes histol&#243;gicos&#46; Esses foram tratados por m&#233;todos convencionais de IHQ&#44; utilizando Polymers &#40;Kit Novolink&#44; Novocastra Laboratories&#44; Newcastle&#8208;upon&#8208;Tyne&#44; Reino Unido&#41; ou o m&#233;todo de estreptavidina&#8208;biotina&#8208;peroxidase de r&#225;bano &#40;LSAB&#8208;HRP&#44; c&#243;digo 0609&#44; Dako Cytomation&#44; Glostrup&#44; Dinamarca&#41;&#46; Cortes histol&#243;gicos de linfonodos&#44; ap&#234;ndice e tonsilas foram usados como controles&#46; Anticorpos prim&#225;rios&#44; m&#233;todo de recupera&#231;&#227;o e sistema de detec&#231;&#227;o empregados s&#227;o detalhados na <a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 2</a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Biomarcadores foram utilizados para avaliar respostas citot&#243;xicas&#44; inflamat&#243;rias e anti&#8208;inflamat&#243;rias&#46; Para a an&#225;lise de ICAM&#8208;1&#44; CD4&#44; CD8&#44; CD25&#44; CD56&#44; granzima A&#44; granzima B&#44; granulisina&#44; perforina e FOXP3&#44; foram escolhidos tr&#234;s campos &#40;400<span class="elsevierStyleHsp" style=""></span>&#215;&#41; com maior densidade de c&#233;lulas inflamat&#243;rias e sem artefatos&#46; Suas imagens digitais foram adquiridas e analisadas com o aux&#237;lio do <span class="elsevierStyleItalic">software</span> Image J &#40;programa de processamento de imagem baseado em Java&#44; Wayne Rasband&#44; NIH&#44; Bethesda&#44; EUA&#44; dispon&#237;vel em <a href="http://rsb.info.nih.gov/ij">http&#58;&#47;&#47;rsb&#46;info&#46;nih&#46;gov&#47;ij</a>&#41;&#46; Tanto as c&#233;lulas imunomarcadas quanto as demais&#44; presentes no mesmo campo&#44; foram contadas&#46; A express&#227;o de cada marcador foi ent&#227;o definida como a raz&#227;o entre o n&#250;mero de c&#233;lulas imunomarcadas e o n&#250;mero total de c&#233;lulas contadas&#46; Para os marcadores IL&#8208;6&#44; IL&#8208;1&#946;&#44; IL&#8208;17&#44; IL&#8208;18 e IL&#8208;10&#44; foi utilizado o m&#233;todo de an&#225;lise descrito por Popovic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A m&#233;dia de idade dos 59 pacientes foi de 39 anos&#59; 55 eram do sexo feminino &#40;93&#44;2&#37;&#41;&#59; 21 tinham LED&#44; 21 tinham l&#250;pus t&#250;mido &#40;LT&#41; e 17 tinham l&#250;pus subagudo &#40;LSA&#41;&#46; Dezenove por cento dos pacientes com LED e LT apresentaram caracter&#237;sticas cl&#237;nicas de envolvimento sist&#234;mico&#44; como classificado pelos crit&#233;rios do ACR&#8208;82 e SLICC&#8208;12&#46; Em rela&#231;&#227;o aos pacientes com LSA&#44; 47&#37; foram classificados como sist&#234;micos de acordo com a classifica&#231;&#227;o SLICC&#8208;12&#59; em contraste&#44; 70&#44;5&#37; dos mesmos pacientes foram classificados como tendo envolvimento sist&#234;mico pelas diretrizes do ACR&#8208;82 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Essa diferen&#231;a ocorreu porque o SLICC&#8208;12 n&#227;o inclui a fotossensibilidade como crit&#233;rio&#44; enquanto o ACR&#8208;82 n&#227;o considera crit&#233;rios de sinovite e teste de Coombs positivo&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Para an&#225;lise estat&#237;stica&#44; foi utilizado o <span class="elsevierStyleItalic">software</span> SAS 9&#46;0&#174;&#46; A an&#225;lise explorat&#243;ria dos dados foi realizada por meio de medidas sum&#225;rias &#40;m&#233;dia&#44; desvio padr&#227;o&#44; m&#237;nimo&#44; mediana&#44; m&#225;ximo&#44; frequ&#234;ncia e percentual&#41;&#46; Os grupos &#40;pacientes com LES<span class="elsevierStyleSup">&#43;</span> e LES<span class="elsevierStyleSup">&#8722;</span>&#41; foram comparados pelo teste exato de Fisher&#44; qui&#8208;quadrado ou Mann&#8208;Whitney&#46; A correla&#231;&#227;o entre as vari&#225;veis num&#233;ricas foi avaliada por meio do coeficiente de Spearman&#46; O n&#237;vel de signific&#226;ncia adotado foi de 5&#37;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo Comit&#234; de &#201;tica da institui&#231;&#227;o &#40;n&#176; 1214&#47;2010&#41;&#44; no qual foram observados todos os princ&#237;pios da Declara&#231;&#227;o de Helsinque&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Em todas as amostras&#44; as c&#233;lulas foram imunomarcadas por todos os anticorpos &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 1</a>&#41;&#44; mas para alguns marcadores houve diferen&#231;as estatisticamente significantes entre os grupos LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; como detalhado na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Em pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span>&#44; classificados por ambos os sistemas&#44; houve maior express&#227;o de IL&#8208;1&#946; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1A e B</a>&#59; ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0143&#41;&#44; em compara&#231;&#227;o com pacientes LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#46; Em rela&#231;&#227;o aos marcadores de resposta T citot&#243;xica&#44; os pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> apresentaram n&#250;mero significantemente maior de c&#233;lulas marcadas com granzima B e perforina &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41; do que os pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0097&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0148&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Pacientes classificados por ambos os sistemas como LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> apresentaram maior express&#227;o de IL&#8208;17 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1C e D</a>&#59; ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0003&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0351&#41;&#46; Al&#233;m disso&#44; houve correla&#231;&#227;o positiva entre a densidade de c&#233;lulas granzima A e FoxP3 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0257&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0285&#41; assim como com as c&#233;lulas CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0075&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0102&#41;&#44; bem como entre c&#233;lulas granulisina e CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0116&#41;&#46; Tamb&#233;m houve correla&#231;&#227;o negativa entre a densidade de c&#233;lulas positivas para granulisina e os seguintes crit&#233;rios de LES &#40;SLICC&#8208;12&#41;&#58; sinovite &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0466&#41;&#44; hipocomplementemia &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0408&#41; e anticorpo anti&#8208;Sm &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0252&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os macr&#243;fagos&#44; entre outras c&#233;lulas&#44; secretam IL&#8208;1&#946; por meio de diferentes est&#237;mulos&#44; principalmente o interferon&#8208;alfa &#40;IFN&#8208;&#945;&#41;&#46; A import&#226;ncia de uma resposta pr&#243;&#8208;inflamat&#243;ria estimulada por IFN tipo I&#44; particularmente IFN&#8208;&#945;&#44; em pacientes com LES&#44; &#233; corroborada por par&#226;metros cl&#237;nicos&#44; como sintomas sist&#234;micos &#40;febre e fadiga&#41;&#44; histopatologia da pele e achados de necropsia&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#8211;9</span></a> Wenzel et al&#46; mostraram que pacientes com les&#245;es discoides disseminadas ou LSA apresentavam n&#237;veis s&#233;ricos aumentados de IFN tipo I&#44; o que pode indicar risco aumentado de desenvolver doen&#231;a sist&#234;mica&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> Na pele&#44; o IFN pode estimular a s&#237;ntese e a superexpress&#227;o de receptores de citocinas que promovem o influxo de c&#233;lulas imunes e o desenvolvimento de les&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Na presente amostra&#44; essa resposta pr&#243;&#8208;inflamat&#243;ria em indiv&#237;duos com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> foi identificada pela express&#227;o de IL&#8208;1&#946; em biopsias de pele&#46; Zhou et al&#46; encontraram n&#237;veis s&#233;ricos aumentados de IL&#8208;1&#946; em pacientes com LES avaliados por citometria de esferas&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> mostrando atividade desregulada das c&#233;lulas T&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Em contraste&#44; em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; o marcador de resposta inflamat&#243;ria foi a IL&#8208;17&#46; Estudos examinando o papel da IL&#8208;17 no l&#250;pus eritematoso&#44; para investigar a efic&#225;cia de medicamentos imunobiol&#243;gicos anti&#8208;IL&#8208;17&#44; relataram aumento na express&#227;o de IL&#8208;17 em les&#245;es de pacientes com LSA e LED e na pele n&#227;o afetada de pacientes com LES&#44; em compara&#231;&#227;o com controles saud&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;13</span></a> Na presente amostra&#44; a express&#227;o de IL&#8208;17 foi significantemente maior em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; sugerindo que medicamentos anti&#8208;IL&#8208;17 poderiam ser eficazes para les&#245;es de LEC&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Em pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> com qualquer subtipo de LEC&#44; identificamos resposta T citot&#243;xica pelo aumento da express&#227;o de granzima B e perforina&#44; necess&#225;rios para a penetra&#231;&#227;o nas c&#233;lulas&#8208;alvo&#46; Granzima B &#233; fortemente expressa na cicatriza&#231;&#227;o de les&#245;es de LEC e est&#225; significantemente aumentada em compara&#231;&#227;o com LSA e controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> Grassi et al&#46; demonstraram que a express&#227;o de c&#233;lulas granzima B positivas era mais frequente na histopatologia da pele de pacientes com LES<span class="elsevierStyleSup">&#43;</span>&#44; em compara&#231;&#227;o com pacientes puramente com LEC&#44; sugerindo que a granzima B &#233; marcador de citotoxicidade chave em indiv&#237;duos com LES&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> Seu papel na g&#234;nese de m&#250;ltiplas manifesta&#231;&#245;es de LES tamb&#233;m &#233; corroborado pelos n&#237;veis mais altos de granzima B s&#233;rica sol&#250;vel em pacientes com LES&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; a correla&#231;&#227;o positiva entre a densidade de c&#233;lulas positivas para CD8&#44; granzima A e granulisina destaca a import&#226;ncia da citotoxicidade na patog&#234;nese das les&#245;es cut&#226;neas&#46; Estudos anteriores mostraram predomin&#226;ncia de c&#233;lulas CD8<span class="elsevierStyleSup">&#43;</span> nas les&#245;es de pacientes com LED&#44; enquanto em outros subtipos de pele mais frequentemente associados a doen&#231;as sist&#234;micas&#44; como LSA&#44; h&#225; predomin&#226;ncia de c&#233;lulas CD4<span class="elsevierStyleSup">&#43;</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">17&#44;18</span></a> Outros estudos enfatizaram apenas o papel da granzima B nas les&#245;es do LEC&#44; sem considerar a poss&#237;vel associa&#231;&#227;o com doen&#231;a sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">14&#44;18</span></a> A granzima A associada &#224; express&#227;o da IL&#8208;17 foi anteriormente descrita em les&#245;es psori&#225;sicas&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> o que pode indicar&#44; no ambiente psori&#225;sico&#44; papel predominante na manuten&#231;&#227;o da inflama&#231;&#227;o&#44; em vez de citotoxicidade&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Os pacientes da presente amostra foram avaliados em um momento espec&#237;fico de sua evolu&#231;&#227;o&#44; quando seus sintomas&#44; sinais e resultados laboratoriais poderiam classific&#225;&#8208;los como pacientes LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> ou LEC&#47;LES<span class="elsevierStyleSup">&#43;</span>&#46; N&#227;o &#233; poss&#237;vel prever quantos mais&#44; de cada grupo&#44; teriam evolu&#237;do para doen&#231;a sist&#234;mica nos pr&#243;ximos cinco ou dez anos&#46; Os autores acreditam que a probabilidade de desenvolver l&#250;pus sist&#234;mico &#233; maior no grupo com LSA&#44; e n&#227;o &#233; poss&#237;vel excluir com seguran&#231;a a possibilidade de que as diferen&#231;as encontradas possam refletir apenas aquelas entre LED&#47;LT e LSA&#46; &#201; importante ressaltar que n&#227;o foram realizadas an&#225;lises comparativas entre os subgrupos de LEC&#44; pois o objetivo principal do presente estudo foi avaliar as diferen&#231;as entre pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; independentemente do subtipo de LEC&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">Na presente amostra&#44; os achados IHQ sugerem que os pacientes com tend&#234;ncia &#224; doen&#231;a sist&#234;mica apresentar&#227;o forte reatividade &#224; IL&#8208;1&#946;&#44; enquanto aqueles com acometimento puramente cut&#226;neo tender&#227;o a expressar mais intensamente a IL&#8208;17&#46; Os achados podem ajudar&#44; juntamente com dados cl&#237;nicos&#44; a identificar pacientes com LEC com maior probabilidade de evoluir para doen&#231;a sist&#234;mica&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">Este trabalho recebeu suporte financeiro da Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo &#40;FAPESP&#41; &#8211; Processo n&#176; 11&#47;50037&#8208;2 e n&#176; 2016&#47;153362&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">B&#225;rbara Hartung Lovato&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Let&#237;cia Fogagnolo&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Elemir Macedo de Souza&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Larissa Juliana Batista da Silva&#58; Revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Paulo Eduardo Neves Ferreira Velho&#58; Revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Maria Let&#237;cia Cintra&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Fernanda Teixeira&#58; Revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Apenas uma fra&#231;&#227;o dos pacientes com l&#250;pus eritematoso cut&#226;neo &#40;LEC&#41; eventualmente evoluir&#225; para doen&#231;a sist&#234;mica &#40;l&#250;pus eritematoso sist&#234;mico &#8211; LES&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Encontrar biomarcadores inflamat&#243;rios que possam predizer a progress&#227;o do LEC para LES utilizando ensaios imuno&#8208;histoqu&#237;micos &#40;IHQ&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Marcadores IHQ para respostas citot&#243;xicas&#44; inflamat&#243;rias e anti&#8208;inflamat&#243;rias e m&#233;todos morfom&#233;tricos foram aplicados a cortes histol&#243;gicos de biopsias de pele emblocadas em parafina&#44; obtidas de les&#245;es de 59 pacientes com l&#250;pus discoide&#44; l&#250;pus subagudo e l&#250;pus t&#250;mido&#46; Para o diagn&#243;stico de LES&#44; os pacientes foram classificados pelos sistemas do American College of Rheumatology &#40;ACR&#8208;82&#41; e do Systemic Lupus International Collaborating Clinics &#40;SLICC&#8208;12&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As amostras de pele de pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> apresentaram maior express&#227;o de IL&#8208;1&#946; &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0143&#41; e n&#250;mero significantemente maior de c&#233;lulas marcadas com granzima B e perforina &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0097&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0148&#41;&#46; Biopsias de indiv&#237;duos com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> apresentaram maior express&#227;o de IL&#8208;17 &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0003&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0351&#41; e correla&#231;&#227;o positiva entre a densidade de c&#233;lulas positivas para granzima A&#44; e para FoxP3<span class="elsevierStyleHsp" style=""></span>&#43; &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0257&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0285&#41; e c&#233;lulas CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0075&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0102&#41;&#44; bem como entre c&#233;lulas positivas para granulisina e CD8 &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0116&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Os pacientes foram avaliados em momento espec&#237;fico de sua evolu&#231;&#227;o e de acordo com a presen&#231;a ou n&#227;o de doen&#231;a sist&#234;mica&#46; N&#227;o podemos prever quantos mais&#44; de cada grupo&#44; teriam evolu&#237;do para LES nos anos seguintes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Nesta coorte&#44; os achados IHQ sugeriram que pacientes com tend&#234;ncia a doen&#231;a sist&#234;mica apresentar&#227;o forte reatividade &#224; IL&#8208;1&#946;&#44; enquanto aqueles com envolvimento puramente cut&#226;neo tender&#227;o a expressar IL&#8208;17 de maneira mais intensa&#46;</p></span>"
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          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Achados imuno&#8208;histoqu&#237;micos&#46; &#40;A&#8211;B&#41; IL&#8208;1&#946;&#46; &#40;C&#8211;D&#41; IL&#8208;17&#46; A&#8211;C&#44; pacientes com LES&#59; B&#8211;D&#44; pacientes com les&#245;es de l&#250;pus eritematoso puramente cut&#226;neo &#40;Aumento original&#58; A<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>&#215;&#59; B&#8211;D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>400<span class="elsevierStyleHsp" style=""></span>&#215;&#41;&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&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">25&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></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">Anti&#8208;DNA &#40;&#37;&#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">75&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">75&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">25&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">25&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></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">SAL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#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"><span class="elsevierStyleBold">12 &#40;70&#44;5&#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"><span class="elsevierStyleBold">5 &#40;29&#44;4&#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"><span class="elsevierStyleBold">8 &#40;47&#44;05&#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"><span class="elsevierStyleBold">9 &#40;52&#44;9&#41;</span>&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">M&#233;dia de idade&#44; anos&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&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&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">39&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">41&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">Sexo&#44; feminino &#40;&#37;&#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">75&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">100&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">75&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">89&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">FAN positivo &#40;&#37;&#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">100&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">60&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">100&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">78&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">Anti&#8208;DNA positivo &#40;&#37;&#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">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">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">51&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">17&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">25&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></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">LT &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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"><span class="elsevierStyleBold">4 &#40;19&#44;04&#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"><span class="elsevierStyleBold">17 &#40;80&#44;9&#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"><span class="elsevierStyleBold">4 &#40;19&#44;04&#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"><span class="elsevierStyleBold">17 &#40;80&#44;9&#41;</span>&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">M&#233;dia de idade&#44; anos&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&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">35&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">39&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">35&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">Sexo&#44; feminino &#40;&#37;&#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">100&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">94&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">100&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">94&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">FAN positivo &#40;&#37;&#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">100&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">30&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">100&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">30&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">Anti&#8208;DNA positivo &#40;&#37;&#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">25&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">25&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">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
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                  \t\t\t\t">17 &#40;85&#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">14 &#40;35&#44;9&#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="" valign="\n
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                  \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">2 &#40;moderado a acentuado&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;15&#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">25 &#40;64&#44;1&#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="" 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" 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">&#37; de c&#233;lulas com imunomarca&#231;&#227;o de CD56 em tr&#234;s campos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" 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</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;1&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  " align="" valign="\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; de c&#233;lulas com imunomarca&#231;&#227;o de ICAM em tr&#234;s campos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t">47&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;7&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">41&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;7&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3426294.png"
              ]
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LEC&#47;LES<span class="elsevierStyleSup"><span class="elsevierStyleBold">&#8722;</span></span>&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>43&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;17 &#40;c&#233;lulas epid&#233;rmicas&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t">2 &#40;moderado&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;76&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;acentuado&#41;&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">10 &#40;23&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">IL&#8208;17 &#40;intersticial&#41;&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Correla&#231;&#227;o entre FoxP3 e granzima A&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&#44;0257&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&#44;0285&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
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                  \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  " align="left" valign="\n
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                      "titulo" => "The 1982 revised criteria for the classification of systemic lupus erythematosus"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Tan"
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                            2 => "J&#46;F&#46; Fries"
                            3 => "A&#46;T&#46; Masi"
                            4 => "D&#46;J&#46; McShane"
                            5 => "N&#46;F&#46; Rothfield"
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                      "doi" => "10.1002/art.1780251101"
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                        "fecha" => "1982"
                        "volumen" => "25"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7138600"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Derivation and validation of Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Petri"
                            1 => "A&#46;-M&#46; Orbai"
                            2 => "G&#46;S&#46; Alarc&#243;n"
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                        "fecha" => "2012"
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                        "paginaFinal" => "2686"
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              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46;F&#46; Chong"
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                            2 => "N&#46;J&#46; Olsen"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2133.2011.10610.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2012"
                        "volumen" => "166"
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IL‐1β e IL‐17 em biopsias de pele de lúpus eritematoso cutâneo: a imuno‐histoquímica poderia indicar tendência ao envolvimento sistêmico?
Barbara Hartung Lovatoa,
Corresponding author
bhlovato@gmail.com

Autor para correspondência.
, Leticia Fogagnoloa, Elemir Macedo de Souzab, Larissa Juliana Batista da Silvaa, Paulo Eduardo Neves Ferreira Velhob, Maria Leticia Cintraa, Fernanda Teixeiraa
a Departamento de Patologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
b Departamento de Dermatologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">Dentre os crit&#233;rios listados tanto pelo <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#8208;82&#41; quanto pelo <span class="elsevierStyleItalic">Systemic Lupus International Collaborating Clinics</span> &#40;SLICC&#8208;12&#41; para o diagn&#243;stico de l&#250;pus eritematoso sist&#234;mico &#40;LES&#41;&#44; quatro est&#227;o relacionados a altera&#231;&#245;es na pele e mucosas&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1&#44;2</span></a> L&#250;pus eritematoso cut&#226;neo &#40;LEC&#41; &#233; um dos achados mais evidentes&#44; mas apenas uma fra&#231;&#227;o dos pacientes com LEC ir&#225; eventualmente desenvolver LES&#58; entre os pacientes com l&#250;pus eritematoso discoide &#40;LED&#41;&#44; o subtipo mais comum de LEC&#44; a frequ&#234;ncia de progress&#227;o para LES varia de 0&#37; a 28&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> As caracter&#237;sticas que levam o m&#233;dico a suspeitar que isso possa acontecer incluem o n&#250;mero e a gravidade das les&#245;es cut&#226;neas&#44; o t&#237;tulo de anticorpos antinucleares e a presen&#231;a de sintomas sist&#234;micos no in&#237;cio da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> A possibilidade de progress&#227;o para LES causa ansiedade em pacientes com l&#250;pus cut&#226;neo&#46; &#201; importante&#44; ent&#227;o&#44; tentar determinar quais pacientes t&#234;m maior risco de progress&#227;o para doen&#231;a sist&#234;mica&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Pesquisas anteriores mostraram a import&#226;ncia das vias pr&#243;&#8208;inflamat&#243;rias e citot&#243;xicas na g&#234;nese do l&#250;pus eritematoso&#44; geralmente comparando os subtipos de LEC&#46; Entretanto&#44; poucos estudos t&#234;m se concentrado nas diferen&#231;as entre pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e aqueles LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#46; O objetivo do presente estudo foi encontrar biomarcadores inflamat&#243;rios que pudessem predizer a progress&#227;o do LEC para LES&#46; Com esse prop&#243;sito&#44; foram utilizados ensaios imuno&#8208;histoqu&#237;micos &#40;IHQ&#41; em biopsias de pele de pacientes com LEC &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 1</a>&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Biopsias de pele de 59 pacientes com LEC atendidos no Ambulat&#243;rio de Dermatologia entre 1995 e 2012 foram inclu&#237;das se&#58; 1&#41; registros m&#233;dicos completos estivessem dispon&#237;veis&#59; 2&#41; o diagn&#243;stico tivesse sido confirmado por exame cl&#237;nico e histopatol&#243;gico&#44; incluindo imunofluoresc&#234;ncia direta&#44; quando indicada&#59; e 3&#41; houvesse tecido suficiente no bloco de parafina para novos cortes histol&#243;gicos&#46; Esses foram tratados por m&#233;todos convencionais de IHQ&#44; utilizando Polymers &#40;Kit Novolink&#44; Novocastra Laboratories&#44; Newcastle&#8208;upon&#8208;Tyne&#44; Reino Unido&#41; ou o m&#233;todo de estreptavidina&#8208;biotina&#8208;peroxidase de r&#225;bano &#40;LSAB&#8208;HRP&#44; c&#243;digo 0609&#44; Dako Cytomation&#44; Glostrup&#44; Dinamarca&#41;&#46; Cortes histol&#243;gicos de linfonodos&#44; ap&#234;ndice e tonsilas foram usados como controles&#46; Anticorpos prim&#225;rios&#44; m&#233;todo de recupera&#231;&#227;o e sistema de detec&#231;&#227;o empregados s&#227;o detalhados na <a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 2</a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Biomarcadores foram utilizados para avaliar respostas citot&#243;xicas&#44; inflamat&#243;rias e anti&#8208;inflamat&#243;rias&#46; Para a an&#225;lise de ICAM&#8208;1&#44; CD4&#44; CD8&#44; CD25&#44; CD56&#44; granzima A&#44; granzima B&#44; granulisina&#44; perforina e FOXP3&#44; foram escolhidos tr&#234;s campos &#40;400<span class="elsevierStyleHsp" style=""></span>&#215;&#41; com maior densidade de c&#233;lulas inflamat&#243;rias e sem artefatos&#46; Suas imagens digitais foram adquiridas e analisadas com o aux&#237;lio do <span class="elsevierStyleItalic">software</span> Image J &#40;programa de processamento de imagem baseado em Java&#44; Wayne Rasband&#44; NIH&#44; Bethesda&#44; EUA&#44; dispon&#237;vel em <a href="http://rsb.info.nih.gov/ij">http&#58;&#47;&#47;rsb&#46;info&#46;nih&#46;gov&#47;ij</a>&#41;&#46; Tanto as c&#233;lulas imunomarcadas quanto as demais&#44; presentes no mesmo campo&#44; foram contadas&#46; A express&#227;o de cada marcador foi ent&#227;o definida como a raz&#227;o entre o n&#250;mero de c&#233;lulas imunomarcadas e o n&#250;mero total de c&#233;lulas contadas&#46; Para os marcadores IL&#8208;6&#44; IL&#8208;1&#946;&#44; IL&#8208;17&#44; IL&#8208;18 e IL&#8208;10&#44; foi utilizado o m&#233;todo de an&#225;lise descrito por Popovic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A m&#233;dia de idade dos 59 pacientes foi de 39 anos&#59; 55 eram do sexo feminino &#40;93&#44;2&#37;&#41;&#59; 21 tinham LED&#44; 21 tinham l&#250;pus t&#250;mido &#40;LT&#41; e 17 tinham l&#250;pus subagudo &#40;LSA&#41;&#46; Dezenove por cento dos pacientes com LED e LT apresentaram caracter&#237;sticas cl&#237;nicas de envolvimento sist&#234;mico&#44; como classificado pelos crit&#233;rios do ACR&#8208;82 e SLICC&#8208;12&#46; Em rela&#231;&#227;o aos pacientes com LSA&#44; 47&#37; foram classificados como sist&#234;micos de acordo com a classifica&#231;&#227;o SLICC&#8208;12&#59; em contraste&#44; 70&#44;5&#37; dos mesmos pacientes foram classificados como tendo envolvimento sist&#234;mico pelas diretrizes do ACR&#8208;82 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Essa diferen&#231;a ocorreu porque o SLICC&#8208;12 n&#227;o inclui a fotossensibilidade como crit&#233;rio&#44; enquanto o ACR&#8208;82 n&#227;o considera crit&#233;rios de sinovite e teste de Coombs positivo&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Para an&#225;lise estat&#237;stica&#44; foi utilizado o <span class="elsevierStyleItalic">software</span> SAS 9&#46;0&#174;&#46; A an&#225;lise explorat&#243;ria dos dados foi realizada por meio de medidas sum&#225;rias &#40;m&#233;dia&#44; desvio padr&#227;o&#44; m&#237;nimo&#44; mediana&#44; m&#225;ximo&#44; frequ&#234;ncia e percentual&#41;&#46; Os grupos &#40;pacientes com LES<span class="elsevierStyleSup">&#43;</span> e LES<span class="elsevierStyleSup">&#8722;</span>&#41; foram comparados pelo teste exato de Fisher&#44; qui&#8208;quadrado ou Mann&#8208;Whitney&#46; A correla&#231;&#227;o entre as vari&#225;veis num&#233;ricas foi avaliada por meio do coeficiente de Spearman&#46; O n&#237;vel de signific&#226;ncia adotado foi de 5&#37;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo Comit&#234; de &#201;tica da institui&#231;&#227;o &#40;n&#176; 1214&#47;2010&#41;&#44; no qual foram observados todos os princ&#237;pios da Declara&#231;&#227;o de Helsinque&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">Em todas as amostras&#44; as c&#233;lulas foram imunomarcadas por todos os anticorpos &#40;<a class="elsevierStyleCrossRef" href="#sec0065">tabela suplementar 1</a>&#41;&#44; mas para alguns marcadores houve diferen&#231;as estatisticamente significantes entre os grupos LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; como detalhado na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Em pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span>&#44; classificados por ambos os sistemas&#44; houve maior express&#227;o de IL&#8208;1&#946; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1A e B</a>&#59; ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0143&#41;&#44; em compara&#231;&#227;o com pacientes LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#46; Em rela&#231;&#227;o aos marcadores de resposta T citot&#243;xica&#44; os pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> apresentaram n&#250;mero significantemente maior de c&#233;lulas marcadas com granzima B e perforina &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41; do que os pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0097&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0148&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Pacientes classificados por ambos os sistemas como LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> apresentaram maior express&#227;o de IL&#8208;17 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1C e D</a>&#59; ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0003&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0351&#41;&#46; Al&#233;m disso&#44; houve correla&#231;&#227;o positiva entre a densidade de c&#233;lulas granzima A e FoxP3 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0257&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0285&#41; assim como com as c&#233;lulas CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0075&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0102&#41;&#44; bem como entre c&#233;lulas granulisina e CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0116&#41;&#46; Tamb&#233;m houve correla&#231;&#227;o negativa entre a densidade de c&#233;lulas positivas para granulisina e os seguintes crit&#233;rios de LES &#40;SLICC&#8208;12&#41;&#58; sinovite &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0466&#41;&#44; hipocomplementemia &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0408&#41; e anticorpo anti&#8208;Sm &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0252&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os macr&#243;fagos&#44; entre outras c&#233;lulas&#44; secretam IL&#8208;1&#946; por meio de diferentes est&#237;mulos&#44; principalmente o interferon&#8208;alfa &#40;IFN&#8208;&#945;&#41;&#46; A import&#226;ncia de uma resposta pr&#243;&#8208;inflamat&#243;ria estimulada por IFN tipo I&#44; particularmente IFN&#8208;&#945;&#44; em pacientes com LES&#44; &#233; corroborada por par&#226;metros cl&#237;nicos&#44; como sintomas sist&#234;micos &#40;febre e fadiga&#41;&#44; histopatologia da pele e achados de necropsia&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6&#8211;9</span></a> Wenzel et al&#46; mostraram que pacientes com les&#245;es discoides disseminadas ou LSA apresentavam n&#237;veis s&#233;ricos aumentados de IFN tipo I&#44; o que pode indicar risco aumentado de desenvolver doen&#231;a sist&#234;mica&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> Na pele&#44; o IFN pode estimular a s&#237;ntese e a superexpress&#227;o de receptores de citocinas que promovem o influxo de c&#233;lulas imunes e o desenvolvimento de les&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Na presente amostra&#44; essa resposta pr&#243;&#8208;inflamat&#243;ria em indiv&#237;duos com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> foi identificada pela express&#227;o de IL&#8208;1&#946; em biopsias de pele&#46; Zhou et al&#46; encontraram n&#237;veis s&#233;ricos aumentados de IL&#8208;1&#946; em pacientes com LES avaliados por citometria de esferas&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> mostrando atividade desregulada das c&#233;lulas T&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Em contraste&#44; em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; o marcador de resposta inflamat&#243;ria foi a IL&#8208;17&#46; Estudos examinando o papel da IL&#8208;17 no l&#250;pus eritematoso&#44; para investigar a efic&#225;cia de medicamentos imunobiol&#243;gicos anti&#8208;IL&#8208;17&#44; relataram aumento na express&#227;o de IL&#8208;17 em les&#245;es de pacientes com LSA e LED e na pele n&#227;o afetada de pacientes com LES&#44; em compara&#231;&#227;o com controles saud&#225;veis&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;13</span></a> Na presente amostra&#44; a express&#227;o de IL&#8208;17 foi significantemente maior em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; sugerindo que medicamentos anti&#8208;IL&#8208;17 poderiam ser eficazes para les&#245;es de LEC&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Em pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> com qualquer subtipo de LEC&#44; identificamos resposta T citot&#243;xica pelo aumento da express&#227;o de granzima B e perforina&#44; necess&#225;rios para a penetra&#231;&#227;o nas c&#233;lulas&#8208;alvo&#46; Granzima B &#233; fortemente expressa na cicatriza&#231;&#227;o de les&#245;es de LEC e est&#225; significantemente aumentada em compara&#231;&#227;o com LSA e controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> Grassi et al&#46; demonstraram que a express&#227;o de c&#233;lulas granzima B positivas era mais frequente na histopatologia da pele de pacientes com LES<span class="elsevierStyleSup">&#43;</span>&#44; em compara&#231;&#227;o com pacientes puramente com LEC&#44; sugerindo que a granzima B &#233; marcador de citotoxicidade chave em indiv&#237;duos com LES&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> Seu papel na g&#234;nese de m&#250;ltiplas manifesta&#231;&#245;es de LES tamb&#233;m &#233; corroborado pelos n&#237;veis mais altos de granzima B s&#233;rica sol&#250;vel em pacientes com LES&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Em pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; a correla&#231;&#227;o positiva entre a densidade de c&#233;lulas positivas para CD8&#44; granzima A e granulisina destaca a import&#226;ncia da citotoxicidade na patog&#234;nese das les&#245;es cut&#226;neas&#46; Estudos anteriores mostraram predomin&#226;ncia de c&#233;lulas CD8<span class="elsevierStyleSup">&#43;</span> nas les&#245;es de pacientes com LED&#44; enquanto em outros subtipos de pele mais frequentemente associados a doen&#231;as sist&#234;micas&#44; como LSA&#44; h&#225; predomin&#226;ncia de c&#233;lulas CD4<span class="elsevierStyleSup">&#43;</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">17&#44;18</span></a> Outros estudos enfatizaram apenas o papel da granzima B nas les&#245;es do LEC&#44; sem considerar a poss&#237;vel associa&#231;&#227;o com doen&#231;a sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">14&#44;18</span></a> A granzima A associada &#224; express&#227;o da IL&#8208;17 foi anteriormente descrita em les&#245;es psori&#225;sicas&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> o que pode indicar&#44; no ambiente psori&#225;sico&#44; papel predominante na manuten&#231;&#227;o da inflama&#231;&#227;o&#44; em vez de citotoxicidade&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Os pacientes da presente amostra foram avaliados em um momento espec&#237;fico de sua evolu&#231;&#227;o&#44; quando seus sintomas&#44; sinais e resultados laboratoriais poderiam classific&#225;&#8208;los como pacientes LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> ou LEC&#47;LES<span class="elsevierStyleSup">&#43;</span>&#46; N&#227;o &#233; poss&#237;vel prever quantos mais&#44; de cada grupo&#44; teriam evolu&#237;do para doen&#231;a sist&#234;mica nos pr&#243;ximos cinco ou dez anos&#46; Os autores acreditam que a probabilidade de desenvolver l&#250;pus sist&#234;mico &#233; maior no grupo com LSA&#44; e n&#227;o &#233; poss&#237;vel excluir com seguran&#231;a a possibilidade de que as diferen&#231;as encontradas possam refletir apenas aquelas entre LED&#47;LT e LSA&#46; &#201; importante ressaltar que n&#227;o foram realizadas an&#225;lises comparativas entre os subgrupos de LEC&#44; pois o objetivo principal do presente estudo foi avaliar as diferen&#231;as entre pacientes LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> e LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span>&#44; independentemente do subtipo de LEC&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">Na presente amostra&#44; os achados IHQ sugerem que os pacientes com tend&#234;ncia &#224; doen&#231;a sist&#234;mica apresentar&#227;o forte reatividade &#224; IL&#8208;1&#946;&#44; enquanto aqueles com acometimento puramente cut&#226;neo tender&#227;o a expressar mais intensamente a IL&#8208;17&#46; Os achados podem ajudar&#44; juntamente com dados cl&#237;nicos&#44; a identificar pacientes com LEC com maior probabilidade de evoluir para doen&#231;a sist&#234;mica&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">Este trabalho recebeu suporte financeiro da Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo &#40;FAPESP&#41; &#8211; Processo n&#176; 11&#47;50037&#8208;2 e n&#176; 2016&#47;153362&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">B&#225;rbara Hartung Lovato&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Let&#237;cia Fogagnolo&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Elemir Macedo de Souza&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Larissa Juliana Batista da Silva&#58; Revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Paulo Eduardo Neves Ferreira Velho&#58; Revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Maria Let&#237;cia Cintra&#58; Concep&#231;&#227;o e planejamento do estudo&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Fernanda Teixeira&#58; Revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Apenas uma fra&#231;&#227;o dos pacientes com l&#250;pus eritematoso cut&#226;neo &#40;LEC&#41; eventualmente evoluir&#225; para doen&#231;a sist&#234;mica &#40;l&#250;pus eritematoso sist&#234;mico &#8211; LES&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Encontrar biomarcadores inflamat&#243;rios que possam predizer a progress&#227;o do LEC para LES utilizando ensaios imuno&#8208;histoqu&#237;micos &#40;IHQ&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Marcadores IHQ para respostas citot&#243;xicas&#44; inflamat&#243;rias e anti&#8208;inflamat&#243;rias e m&#233;todos morfom&#233;tricos foram aplicados a cortes histol&#243;gicos de biopsias de pele emblocadas em parafina&#44; obtidas de les&#245;es de 59 pacientes com l&#250;pus discoide&#44; l&#250;pus subagudo e l&#250;pus t&#250;mido&#46; Para o diagn&#243;stico de LES&#44; os pacientes foram classificados pelos sistemas do American College of Rheumatology &#40;ACR&#8208;82&#41; e do Systemic Lupus International Collaborating Clinics &#40;SLICC&#8208;12&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As amostras de pele de pacientes com LEC&#47;LES<span class="elsevierStyleSup">&#43;</span> apresentaram maior express&#227;o de IL&#8208;1&#946; &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0143&#41; e n&#250;mero significantemente maior de c&#233;lulas marcadas com granzima B e perforina &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0097&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0148&#41;&#46; Biopsias de indiv&#237;duos com LEC&#47;LES<span class="elsevierStyleSup">&#8722;</span> apresentaram maior express&#227;o de IL&#8208;17 &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0003&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0351&#41; e correla&#231;&#227;o positiva entre a densidade de c&#233;lulas positivas para granzima A&#44; e para FoxP3<span class="elsevierStyleHsp" style=""></span>&#43; &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0257&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0285&#41; e c&#233;lulas CD8 positivas &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0075&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0102&#41;&#44; bem como entre c&#233;lulas positivas para granulisina e CD8 &#40;ACR&#8208;82&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0024&#59; SLICC&#8208;12&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0116&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Os pacientes foram avaliados em momento espec&#237;fico de sua evolu&#231;&#227;o e de acordo com a presen&#231;a ou n&#227;o de doen&#231;a sist&#234;mica&#46; N&#227;o podemos prever quantos mais&#44; de cada grupo&#44; teriam evolu&#237;do para LES nos anos seguintes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Nesta coorte&#44; os achados IHQ sugeriram que pacientes com tend&#234;ncia a doen&#231;a sist&#234;mica apresentar&#227;o forte reatividade &#224; IL&#8208;1&#946;&#44; enquanto aqueles com envolvimento puramente cut&#226;neo tender&#227;o a expressar IL&#8208;17 de maneira mais intensa&#46;</p></span>"
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          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Achados imuno&#8208;histoqu&#237;micos&#46; &#40;A&#8211;B&#41; IL&#8208;1&#946;&#46; &#40;C&#8211;D&#41; IL&#8208;17&#46; A&#8211;C&#44; pacientes com LES&#59; B&#8211;D&#44; pacientes com les&#245;es de l&#250;pus eritematoso puramente cut&#226;neo &#40;Aumento original&#58; A<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>&#215;&#59; B&#8211;D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>400<span class="elsevierStyleHsp" style=""></span>&#215;&#41;&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&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">25&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></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">Anti&#8208;DNA &#40;&#37;&#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">75&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">75&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">25&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">25&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></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">SAL &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#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"><span class="elsevierStyleBold">12 &#40;70&#44;5&#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"><span class="elsevierStyleBold">5 &#40;29&#44;4&#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"><span class="elsevierStyleBold">8 &#40;47&#44;05&#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"><span class="elsevierStyleBold">9 &#40;52&#44;9&#41;</span>&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">M&#233;dia de idade&#44; anos&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&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&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">39&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">41&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">Sexo&#44; feminino &#40;&#37;&#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">75&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">100&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">75&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">89&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">FAN positivo &#40;&#37;&#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">100&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">60&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">100&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">78&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">Anti&#8208;DNA positivo &#40;&#37;&#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">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">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">51&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">17&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">25&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></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">LT &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#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"><span class="elsevierStyleBold">4 &#40;19&#44;04&#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"><span class="elsevierStyleBold">17 &#40;80&#44;9&#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"><span class="elsevierStyleBold">4 &#40;19&#44;04&#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"><span class="elsevierStyleBold">17 &#40;80&#44;9&#41;</span>&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">M&#233;dia de idade&#44; anos&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&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">35&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">39&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">35&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">Sexo&#44; feminino &#40;&#37;&#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">100&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">94&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">100&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">94&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">FAN positivo &#40;&#37;&#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">100&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">30&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">100&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">30&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">Anti&#8208;DNA positivo &#40;&#37;&#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">25&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">25&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></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">Anti&#8208;Sm positivo &#40;&#37;&#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">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
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                  \t\t\t\t">17 &#40;85&#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">14 &#40;35&#44;9&#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="" valign="\n
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                  \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">2 &#40;moderado a acentuado&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;15&#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">25 &#40;64&#44;1&#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="" 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" 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">&#37; de c&#233;lulas com imunomarca&#231;&#227;o de CD56 em tr&#234;s campos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" 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</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;1&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  " align="" valign="\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; de c&#233;lulas com imunomarca&#231;&#227;o de ICAM em tr&#234;s campos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t">47&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;7&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">41&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;7&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3426294.png"
              ]
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LEC&#47;LES<span class="elsevierStyleSup"><span class="elsevierStyleBold">&#8722;</span></span>&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>43&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;17 &#40;c&#233;lulas epid&#233;rmicas&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t">2 &#40;moderado&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;76&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;acentuado&#41;&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">10 &#40;23&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">IL&#8208;17 &#40;intersticial&#41;&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Correla&#231;&#227;o entre FoxP3 e granzima A&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&#44;0257&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&#44;0285&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
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                  \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  " align="left" valign="\n
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                      "titulo" => "The 1982 revised criteria for the classification of systemic lupus erythematosus"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Tan"
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                            2 => "J&#46;F&#46; Fries"
                            3 => "A&#46;T&#46; Masi"
                            4 => "D&#46;J&#46; McShane"
                            5 => "N&#46;F&#46; Rothfield"
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                      "doi" => "10.1002/art.1780251101"
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                        "fecha" => "1982"
                        "volumen" => "25"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7138600"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Derivation and validation of Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Petri"
                            1 => "A&#46;-M&#46; Orbai"
                            2 => "G&#46;S&#46; Alarc&#243;n"
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                        "fecha" => "2012"
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                        "paginaFinal" => "2686"
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              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46;F&#46; Chong"
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                            2 => "N&#46;J&#46; Olsen"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2133.2011.10610.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2012"
                        "volumen" => "166"
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Article information
ISSN: 26662752
Original language: Portuguese
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2024 July 205 112 317
2024 June 158 81 239
2024 May 81 73 154
2024 April 138 94 232
2024 March 132 77 209
2024 February 138 102 240
2024 January 174 84 258
2023 December 75 51 126
2023 November 105 116 221
2023 October 69 91 160
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