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ou <span class="elsevierStyleItalic">heat shock protein</span>&#160;70 &#40;Hsp70&#41;&#44; &#233; mol&#233;cula chave na resposta imune inata do vitiligo&#44; constituindo&#8208;se uma chaperona intracelular&#44; respons&#225;vel pelo dobramento correto das prote&#237;nas no ret&#237;culo endoplasm&#225;tico e por impedir a agrega&#231;&#227;o de prote&#237;nas mal dobradas&#46; Ela existe naturalmente nos tecidos e pode ser induzida pelo estresse celular&#46; Na fisiopatologia do vitiligo&#44; ap&#243;s um gatilho inicial &#40;radia&#231;&#227;o ultravioleta&#44; trauma ou exposi&#231;&#227;o a compostos fen&#243;licos&#41;&#44; o melan&#243;cito sofre processo de estresse oxidativo&#44; que induz a s&#237;ntese da Hsp70&#46; A partir disso&#44; Hsp70 &#233; secretada para o meio extracelular levando &#224; ativa&#231;&#227;o de c&#233;lulas dendr&#237;ticas&#44; que se transformam em c&#233;lulas apresentadoras de ant&#237;genos&#44; estas que ativam os linf&#243;citos&#160;T&#44; dando in&#237;cio &#224; resposta imune adaptativa&#46; Portanto&#44; no vitiligo&#44; a Hsp70 &#233; considerada um elo entre as respostas imunes inata e adaptativa&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Estudos em modelos animais demonstraram que Hsp70 n&#227;o s&#243; &#233; necess&#225;ria como tamb&#233;m suficiente para desencadear a despigmenta&#231;&#227;o em camundongos predispostos a vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Enquanto os n&#237;veis teciduais da Hsp70 s&#227;o aumentados no vitiligo em atividade&#44; n&#227;o h&#225; estudos que tenham investigado os n&#237;veis circulantes da prote&#237;na nesses pacientes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Conduziu&#8208;se estudo transversal em Curitiba&#44; PR &#40;Brasil&#41;&#44; entre novembro de&#160;2020 a fevereiro de&#160;2022&#44; objetivando determinar os n&#237;veis plasm&#225;ticos de Hsp70 em adultos com vitiligo n&#227;o segmentar n&#227;o submetidos a imunossupress&#227;o&#44; nem portadores de outras doen&#231;as reumatol&#243;gicas&#44; c&#226;ncer ou doen&#231;a inflamat&#243;ria intestinal &#40;DII&#41;&#44; para n&#227;o haver confundimento dos n&#237;veis de Hsp70 por mediadores inflamat&#243;rios&#46; Coletaram&#8208;se dados cl&#237;nicos e amostras de sangue perif&#233;rico dos participantes durante a consulta&#46; Utilizou&#8208;se o kit Hsp70 ELISA &#40;ADI&#8208;EKS&#8208;700B&#44; Enzo Life Sciences&#44; New York&#44; USA&#41; para estimativa do Hsp70 circulante&#46; Os valores obtidos foram comparados entre os subgrupos quanto &#224; atividade da doen&#231;a&#58; est&#225;vel &#40;&#62; 1&#160;ano&#41;&#44; progress&#227;o&#44; e regress&#227;o &#40;em repigmenta&#231;&#227;o&#41;&#59; assim como em rela&#231;&#227;o &#224; extens&#227;o cl&#237;nica&#46; A atividade da doen&#231;a foi determinada por meio do relato do pr&#243;prio paciente&#46; A extens&#227;o da doen&#231;a foi estimada pelo aplicativo &#8220;Vitiligo Calculator&#8221; &#40;<a href="https://www.vitiligo-calculator.com/">https&#58;&#47;&#47;www&#46;vitiligo&#8208;calculator&#46;com</a>&#41;&#44; o qual utiliza o instrumento VES &#40;<span class="elsevierStyleItalic">Vitiligo Extent Score</span>&#41; validado por van Geel et al&#46; O VES baseia&#8208;se em imagens padronizadas com diferentes graus de acometimento cut&#226;neo&#44; em 19 diferentes topografias&#46; Numericamente&#44; o VES pode variar de&#160;zero&#160;a&#160;100&#44; e apresenta alta correla&#231;&#227;o com o VASI&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos no estudo 89 participantes&#59; seus principais dados cl&#237;nicos e demogr&#225;ficos est&#227;o dispostos na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; A maior parte dos indiv&#237;duos estava com a doen&#231;a em progress&#227;o durante a inclus&#227;o&#44; havendo ampla variabilidade da extens&#227;o cl&#237;nica da doen&#231;a &#40;VES variou de&#160;0&#44;04&#160;a&#160;71&#44;06&#41;&#44; e dos n&#237;veis plasm&#225;ticos de Hsp70 &#40;variaram de&#160;1&#44;82&#160;a&#160;27&#44;8&#160;ng&#47;mL&#41;&#46; Foi definido o valor de corte de Hsp70 como&#160;2&#44;8&#160;ng&#47;mL para compara&#231;&#227;o entre os subgrupos&#46; Esse valor foi definido como a melhor separa&#231;&#227;o entr&#243;pica entre os indiv&#237;duos com e sem atividade de doen&#231;a&#44; j&#225; que n&#227;o h&#225; um padr&#227;o de normalidade na literatura&#44; tanto na popula&#231;&#227;o geral quanto para portadores de vitiligo&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">N&#227;o houve correla&#231;&#227;o direta entre os n&#237;veis de Hsp70 e VES &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;461&#41;&#44; assim como Hsp70 e tempo de doen&#231;a&#44; IMC&#44; idade&#44; fototipo &#40;rho<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;16&#59; p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;1&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Quando considerado o valor de corte da normalidade para Hsp70 como 2&#44;8 ng&#47;mL&#44; 76&#44;9&#37; dos vitiligos em regress&#227;o apresentaram valores alterados&#44; enquanto isso ocorreu em apenas 35&#44;7&#37; dos est&#225;veis e 37&#44;1&#37; dos em progress&#227;o &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;028&#41;&#46; Esse comportamento se comprovou mesmo quando ajustado por sexo&#44; idade&#44; extens&#227;o da doen&#231;a e fototipo &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Valores alterados de Hsp70 n&#227;o se associaram com as comorbidades avaliadas &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;40&#41;&#46; Entre os tratamentos atuais&#44; corticosteroides orais&#44; metotrexato e PUVA n&#227;o se associaram a Hsp70 &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;20&#41;&#59; por&#233;m&#44; os participantes sob fototerapia Nb&#8208;UVB mostraram maior frequ&#234;ncia de positividade para Hsp70&#58; 71&#37;&#160;<span class="elsevierStyleItalic">vs</span>&#46;&#160;36&#37; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;2&#59; 95&#37;IC&#160;1&#44;3&#8208;13&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;010&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Embora alguns estudos tenham demonstrado aumento da Hsp70 tecidual na pele lesional e perilesional de vitiligo em atividade&#44; at&#233; o momento ainda n&#227;o haviam sido avaliados os n&#237;veis plasm&#225;ticos dessa prote&#237;na nos portadores da doen&#231;a&#44; tampouco tentado correlacion&#225;&#8208;lo com a atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Em nossa pesquisa&#44; n&#227;o encontramos correla&#231;&#227;o entre n&#237;veis plasm&#225;ticos de Hsp70 e extens&#227;o da doen&#231;a&#59; por&#233;m&#44; a positividade do Hsp70 se associou &#224;s formas regressivas de vitiligo&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Esse achado sugere n&#227;o haver alinhamento entre o comportamento da Hsp70 plasm&#225;tica e sua express&#227;o tecidual da Hsp70&#44; limitando seu uso como marcador direto de gravidade da doen&#231;a&#46; De fato&#44; outras dermatoses inflamat&#243;rias&#44; como psor&#237;ase e dermatite at&#243;pica&#44; tamb&#233;m n&#227;o apresentam forte correla&#231;&#227;o entre marcadores plasm&#225;ticos e extens&#227;o da doen&#231;a&#46; At&#233; o momento&#44; n&#227;o h&#225; estudos em vitiligo no qual&#44; em um mesmo indiv&#237;duo&#44; tenha&#8208;se dosado a Hsp70 plasm&#225;tica e estimado a concentra&#231;&#227;o de Hsp70 tecidual da pele afetada&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Deve&#8208;se&#44; por&#233;m&#44; considerar que a Hsp70 possa desempenhar fun&#231;&#245;es diferentes de acordo com a fase da doen&#231;a&#46; Por exemplo&#44; na artrite reumatoide&#44; diferentes estudos mostraram pap&#233;is contradit&#243;rios da Hsp70 &#8211; ou seja&#44; tanto na promo&#231;&#227;o da inflama&#231;&#227;o&#44; induzindo a produ&#231;&#227;o de citocinas pr&#243;&#8208;inflamat&#243;rias&#44; quanto em sua modula&#231;&#227;o&#44; estimulando a forma&#231;&#227;o de c&#233;lulas&#160;T reguladoras &#40;Tregs&#41; e interrompendo a atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Nas DII&#44; existem evid&#234;ncias de que a Hsp70 tenha sua express&#227;o aumentada na mucosa intestinal&#44; mas a maioria dos estudos aponta para um papel protetor&#44; em que o aumento local da Hsp70 se associou &#224; redu&#231;&#227;o da atividade da doen&#231;a&#44; em modelos experimentais&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> Ademais&#44; foi demonstrado papel importante da Hsp70 na supress&#227;o da resposta imunol&#243;gica por meio da forma&#231;&#227;o de c&#233;lulas B reguladoras &#40;Bregs&#41;&#44; em um estudo experimental que utilizou modelos animais de tireoidite autoimune e DII&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">O modelo fisiopatol&#243;gico do vitiligo &#233; complexo&#46; A disfun&#231;&#227;o das c&#233;lulas&#160;Tregs &#233; uma das vias de manuten&#231;&#227;o da autoimunidade no vitiligo&#46; Por&#233;m&#44; se existe algum papel das c&#233;lulas Bregs no vitiligo e se a Hsp70 circulante participa dessa modula&#231;&#227;o&#44; ainda n&#227;o est&#225; elucidado&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Indiv&#237;duos em tratamento com Nb&#8208;UVB apresentaram maior positividade de Hsp70&#46; Al&#233;m disso&#44; quando utilizado o ponto de corte de&#160;2&#44;8&#160;ng&#47;mL&#44; os n&#237;veis plasm&#225;ticos da Hsp70 se associaram ao vitiligo em regress&#227;o&#46; &#201; poss&#237;vel que a Hsp70 desempenhe diferentes pap&#233;is no vitiligo&#44; dependendo da fase da doen&#231;a&#44; ou que a pr&#243;pria fototerapia Nb&#8208;UVB induza o aumento dos n&#237;veis da Hsp70 circulantes&#46; A associa&#231;&#227;o entre a exposi&#231;&#227;o UVB&#44; n&#237;veis de vitamina D&#44; estresse oxidativo induzido pela fototerapia e os n&#237;veis plasm&#225;ticos de Hsp70 devem ser explorados com desenhos adequados&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Este estudo apresenta limita&#231;&#245;es ligadas &#224; falta da constata&#231;&#227;o da express&#227;o da Hsp70 tecidual nos participantes&#46; Investiga&#231;&#245;es posteriores que explorem os n&#237;veis de Hsp70 plasm&#225;ticos e os mecanismos de toler&#226;ncia imunol&#243;gica em diferentes fases de atividade da doen&#231;a s&#227;o necess&#225;rias para esclarecer o papel da Hsp70 circulante no vitiligo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Em conclus&#227;o&#44; os n&#237;veis plasm&#225;ticos de Hsp70 n&#227;o se correlacionaram diretamente com a extens&#227;o do vitiligo&#59; entretanto&#44; maior positividade foi identificada em participantes com formas regressivas da doen&#231;a&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Aprova&#231;&#227;o pelo Comit&#234; de &#201;tica</span><p id="par0080" class="elsevierStylePara elsevierViewall">Este projeto foi aprovado pelo Comit&#234; de &#201;tica da Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; &#40;parecer n&#250;mero&#160;4&#46;333&#46;389&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">FUNADERM&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">Helena Zenedin Marchioro&#58; Concep&#231;&#227;o do estudo&#59; coleta dos dados&#59; an&#225;lise dos resultados&#59; escrita do texto&#59; revis&#227;o e aprova&#231;&#227;o do texto final&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Caio C&#233;sar Silva de Castro&#58; Concep&#231;&#227;o do estudo&#59; an&#225;lise dos resultados&#59; escrita do texto&#59; revis&#227;o e aprova&#231;&#227;o do texto final&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Isabella Gizzi Jiacomini&#58; Coleta dos dados&#44; an&#225;lise dos resultados&#59; revis&#227;o e aprova&#231;&#227;o final do texto&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do artigo&#59; revis&#227;o cr&#237;tica de 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="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflito de interesses</span><p id="par0110" class="elsevierStylePara elsevierViewall">Helena Zenedin Marchioro&#58; Nenhum&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Caio C&#233;sar Silva de Castro&#58; Ache &#8211; speaker&#44; advisory board&#59; Sun pharma &#8211; advisory board&#59; Abbvie &#8211; advisory board&#59; Pfizer &#8211; clinical trial&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Isabella Gizzi Jiacomini&#58; Nenhum&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Nenhum&#46;</p></span></span>"
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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"><span class="elsevierStyleHsp" style=""></span>IV e V&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">30&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Escolaridade&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fundamental&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">23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dio&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">29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">32&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Superior&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">37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">41&#44;6&#37;&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"><span class="elsevierStyleItalic">IMC &#40;kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#41;&#44; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">27&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbidades&#44; n &#40;&#37;&#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="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hipertens&#227;o arterial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes <span class="elsevierStyleItalic">mellitus</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
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a tireoideana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Depress&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">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
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                  \t\t\t\t">19&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ansiedade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">27&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dislipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade de in&#237;cio do vitiligo&#44; mediana &#40;DIQ&#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">38&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">15&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tempo de doen&#231;a &#40;anos&#41;&#44; m&#233;dia &#40;DP&#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">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tratamentos atuais&#44; n &#40;&#37;&#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="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Corticoide t&#243;pico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inibidor de calcineurina t&#243;pico&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
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                  \t\t\t\t">47&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PUVA&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">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NB&#8208;UVB&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">19&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Atividade da doen&#231;a&#44; n &#40;&#37;&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Regress&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;6&#37;&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Progress&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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Carta ‐ Investigação
Associação entre características clínicas e níveis plasmáticos de Hsp70 em adultos com vitiligo não segmentar: estudo transversal
Helena Zenedin Marchioroa,
Corresponding author
helena.marchioro@unesp.br

Autor para correspondência.
, Caio César Silva de Castroa,b, Isabella Gizzi Jiacominic, Hélio Amante Miotd
a Departamento de Dermatologia, Hospital Santa Casa de Curitiba, Curitiba, PR, Brasil
b Departamento de Dermatologia, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil
c Departamento de Patologia Básica do Setor de Ciências Biológicas da Universidade Federal do Paraná, Curitiba, PR, Brasil
d Departamento de Dermatologia e Radioterapia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Vitiligo &#233; doen&#231;a autoimune sist&#234;mica caracterizada por despigmenta&#231;&#227;o cut&#226;nea&#44; que acomete 0&#44;57&#37; da popula&#231;&#227;o brasileira e corresponde a 1&#44;6&#37; dos atendimentos dermatol&#243;gicos no Brasil&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Sua patog&#234;nese envolve predisposi&#231;&#227;o gen&#233;tica&#44; sensibilidade dos melan&#243;citos ao estresse oxidativo&#44; falhas na ades&#227;o intercelular nos melan&#243;citos e ativa&#231;&#227;o da resposta imunol&#243;gica&#44; o que justifica a maior frequ&#234;ncia de doen&#231;as autoimunes concomitantes&#44; como tireoidopatias&#44; diabetes <span class="elsevierStyleItalic">mellitus</span> e l&#250;pus eritematoso sist&#234;mico&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A prote&#237;na de choque t&#233;rmico&#160;70&#44; ou <span class="elsevierStyleItalic">heat shock protein</span>&#160;70 &#40;Hsp70&#41;&#44; &#233; mol&#233;cula chave na resposta imune inata do vitiligo&#44; constituindo&#8208;se uma chaperona intracelular&#44; respons&#225;vel pelo dobramento correto das prote&#237;nas no ret&#237;culo endoplasm&#225;tico e por impedir a agrega&#231;&#227;o de prote&#237;nas mal dobradas&#46; Ela existe naturalmente nos tecidos e pode ser induzida pelo estresse celular&#46; Na fisiopatologia do vitiligo&#44; ap&#243;s um gatilho inicial &#40;radia&#231;&#227;o ultravioleta&#44; trauma ou exposi&#231;&#227;o a compostos fen&#243;licos&#41;&#44; o melan&#243;cito sofre processo de estresse oxidativo&#44; que induz a s&#237;ntese da Hsp70&#46; A partir disso&#44; Hsp70 &#233; secretada para o meio extracelular levando &#224; ativa&#231;&#227;o de c&#233;lulas dendr&#237;ticas&#44; que se transformam em c&#233;lulas apresentadoras de ant&#237;genos&#44; estas que ativam os linf&#243;citos&#160;T&#44; dando in&#237;cio &#224; resposta imune adaptativa&#46; Portanto&#44; no vitiligo&#44; a Hsp70 &#233; considerada um elo entre as respostas imunes inata e adaptativa&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Estudos em modelos animais demonstraram que Hsp70 n&#227;o s&#243; &#233; necess&#225;ria como tamb&#233;m suficiente para desencadear a despigmenta&#231;&#227;o em camundongos predispostos a vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Enquanto os n&#237;veis teciduais da Hsp70 s&#227;o aumentados no vitiligo em atividade&#44; n&#227;o h&#225; estudos que tenham investigado os n&#237;veis circulantes da prote&#237;na nesses pacientes&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Conduziu&#8208;se estudo transversal em Curitiba&#44; PR &#40;Brasil&#41;&#44; entre novembro de&#160;2020 a fevereiro de&#160;2022&#44; objetivando determinar os n&#237;veis plasm&#225;ticos de Hsp70 em adultos com vitiligo n&#227;o segmentar n&#227;o submetidos a imunossupress&#227;o&#44; nem portadores de outras doen&#231;as reumatol&#243;gicas&#44; c&#226;ncer ou doen&#231;a inflamat&#243;ria intestinal &#40;DII&#41;&#44; para n&#227;o haver confundimento dos n&#237;veis de Hsp70 por mediadores inflamat&#243;rios&#46; Coletaram&#8208;se dados cl&#237;nicos e amostras de sangue perif&#233;rico dos participantes durante a consulta&#46; Utilizou&#8208;se o kit Hsp70 ELISA &#40;ADI&#8208;EKS&#8208;700B&#44; Enzo Life Sciences&#44; New York&#44; USA&#41; para estimativa do Hsp70 circulante&#46; Os valores obtidos foram comparados entre os subgrupos quanto &#224; atividade da doen&#231;a&#58; est&#225;vel &#40;&#62; 1&#160;ano&#41;&#44; progress&#227;o&#44; e regress&#227;o &#40;em repigmenta&#231;&#227;o&#41;&#59; assim como em rela&#231;&#227;o &#224; extens&#227;o cl&#237;nica&#46; A atividade da doen&#231;a foi determinada por meio do relato do pr&#243;prio paciente&#46; A extens&#227;o da doen&#231;a foi estimada pelo aplicativo &#8220;Vitiligo Calculator&#8221; &#40;<a href="https://www.vitiligo-calculator.com/">https&#58;&#47;&#47;www&#46;vitiligo&#8208;calculator&#46;com</a>&#41;&#44; o qual utiliza o instrumento VES &#40;<span class="elsevierStyleItalic">Vitiligo Extent Score</span>&#41; validado por van Geel et al&#46; O VES baseia&#8208;se em imagens padronizadas com diferentes graus de acometimento cut&#226;neo&#44; em 19 diferentes topografias&#46; Numericamente&#44; o VES pode variar de&#160;zero&#160;a&#160;100&#44; e apresenta alta correla&#231;&#227;o com o VASI&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos no estudo 89 participantes&#59; seus principais dados cl&#237;nicos e demogr&#225;ficos est&#227;o dispostos na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; A maior parte dos indiv&#237;duos estava com a doen&#231;a em progress&#227;o durante a inclus&#227;o&#44; havendo ampla variabilidade da extens&#227;o cl&#237;nica da doen&#231;a &#40;VES variou de&#160;0&#44;04&#160;a&#160;71&#44;06&#41;&#44; e dos n&#237;veis plasm&#225;ticos de Hsp70 &#40;variaram de&#160;1&#44;82&#160;a&#160;27&#44;8&#160;ng&#47;mL&#41;&#46; Foi definido o valor de corte de Hsp70 como&#160;2&#44;8&#160;ng&#47;mL para compara&#231;&#227;o entre os subgrupos&#46; Esse valor foi definido como a melhor separa&#231;&#227;o entr&#243;pica entre os indiv&#237;duos com e sem atividade de doen&#231;a&#44; j&#225; que n&#227;o h&#225; um padr&#227;o de normalidade na literatura&#44; tanto na popula&#231;&#227;o geral quanto para portadores de vitiligo&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">N&#227;o houve correla&#231;&#227;o direta entre os n&#237;veis de Hsp70 e VES &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;461&#41;&#44; assim como Hsp70 e tempo de doen&#231;a&#44; IMC&#44; idade&#44; fototipo &#40;rho<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;16&#59; p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;1&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Quando considerado o valor de corte da normalidade para Hsp70 como 2&#44;8 ng&#47;mL&#44; 76&#44;9&#37; dos vitiligos em regress&#227;o apresentaram valores alterados&#44; enquanto isso ocorreu em apenas 35&#44;7&#37; dos est&#225;veis e 37&#44;1&#37; dos em progress&#227;o &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;028&#41;&#46; Esse comportamento se comprovou mesmo quando ajustado por sexo&#44; idade&#44; extens&#227;o da doen&#231;a e fototipo &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Valores alterados de Hsp70 n&#227;o se associaram com as comorbidades avaliadas &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;40&#41;&#46; Entre os tratamentos atuais&#44; corticosteroides orais&#44; metotrexato e PUVA n&#227;o se associaram a Hsp70 &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;20&#41;&#59; por&#233;m&#44; os participantes sob fototerapia Nb&#8208;UVB mostraram maior frequ&#234;ncia de positividade para Hsp70&#58; 71&#37;&#160;<span class="elsevierStyleItalic">vs</span>&#46;&#160;36&#37; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;2&#59; 95&#37;IC&#160;1&#44;3&#8208;13&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;010&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Embora alguns estudos tenham demonstrado aumento da Hsp70 tecidual na pele lesional e perilesional de vitiligo em atividade&#44; at&#233; o momento ainda n&#227;o haviam sido avaliados os n&#237;veis plasm&#225;ticos dessa prote&#237;na nos portadores da doen&#231;a&#44; tampouco tentado correlacion&#225;&#8208;lo com a atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Em nossa pesquisa&#44; n&#227;o encontramos correla&#231;&#227;o entre n&#237;veis plasm&#225;ticos de Hsp70 e extens&#227;o da doen&#231;a&#59; por&#233;m&#44; a positividade do Hsp70 se associou &#224;s formas regressivas de vitiligo&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Esse achado sugere n&#227;o haver alinhamento entre o comportamento da Hsp70 plasm&#225;tica e sua express&#227;o tecidual da Hsp70&#44; limitando seu uso como marcador direto de gravidade da doen&#231;a&#46; De fato&#44; outras dermatoses inflamat&#243;rias&#44; como psor&#237;ase e dermatite at&#243;pica&#44; tamb&#233;m n&#227;o apresentam forte correla&#231;&#227;o entre marcadores plasm&#225;ticos e extens&#227;o da doen&#231;a&#46; At&#233; o momento&#44; n&#227;o h&#225; estudos em vitiligo no qual&#44; em um mesmo indiv&#237;duo&#44; tenha&#8208;se dosado a Hsp70 plasm&#225;tica e estimado a concentra&#231;&#227;o de Hsp70 tecidual da pele afetada&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Deve&#8208;se&#44; por&#233;m&#44; considerar que a Hsp70 possa desempenhar fun&#231;&#245;es diferentes de acordo com a fase da doen&#231;a&#46; Por exemplo&#44; na artrite reumatoide&#44; diferentes estudos mostraram pap&#233;is contradit&#243;rios da Hsp70 &#8211; ou seja&#44; tanto na promo&#231;&#227;o da inflama&#231;&#227;o&#44; induzindo a produ&#231;&#227;o de citocinas pr&#243;&#8208;inflamat&#243;rias&#44; quanto em sua modula&#231;&#227;o&#44; estimulando a forma&#231;&#227;o de c&#233;lulas&#160;T reguladoras &#40;Tregs&#41; e interrompendo a atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Nas DII&#44; existem evid&#234;ncias de que a Hsp70 tenha sua express&#227;o aumentada na mucosa intestinal&#44; mas a maioria dos estudos aponta para um papel protetor&#44; em que o aumento local da Hsp70 se associou &#224; redu&#231;&#227;o da atividade da doen&#231;a&#44; em modelos experimentais&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> Ademais&#44; foi demonstrado papel importante da Hsp70 na supress&#227;o da resposta imunol&#243;gica por meio da forma&#231;&#227;o de c&#233;lulas B reguladoras &#40;Bregs&#41;&#44; em um estudo experimental que utilizou modelos animais de tireoidite autoimune e DII&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">O modelo fisiopatol&#243;gico do vitiligo &#233; complexo&#46; A disfun&#231;&#227;o das c&#233;lulas&#160;Tregs &#233; uma das vias de manuten&#231;&#227;o da autoimunidade no vitiligo&#46; Por&#233;m&#44; se existe algum papel das c&#233;lulas Bregs no vitiligo e se a Hsp70 circulante participa dessa modula&#231;&#227;o&#44; ainda n&#227;o est&#225; elucidado&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Indiv&#237;duos em tratamento com Nb&#8208;UVB apresentaram maior positividade de Hsp70&#46; Al&#233;m disso&#44; quando utilizado o ponto de corte de&#160;2&#44;8&#160;ng&#47;mL&#44; os n&#237;veis plasm&#225;ticos da Hsp70 se associaram ao vitiligo em regress&#227;o&#46; &#201; poss&#237;vel que a Hsp70 desempenhe diferentes pap&#233;is no vitiligo&#44; dependendo da fase da doen&#231;a&#44; ou que a pr&#243;pria fototerapia Nb&#8208;UVB induza o aumento dos n&#237;veis da Hsp70 circulantes&#46; A associa&#231;&#227;o entre a exposi&#231;&#227;o UVB&#44; n&#237;veis de vitamina D&#44; estresse oxidativo induzido pela fototerapia e os n&#237;veis plasm&#225;ticos de Hsp70 devem ser explorados com desenhos adequados&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Este estudo apresenta limita&#231;&#245;es ligadas &#224; falta da constata&#231;&#227;o da express&#227;o da Hsp70 tecidual nos participantes&#46; Investiga&#231;&#245;es posteriores que explorem os n&#237;veis de Hsp70 plasm&#225;ticos e os mecanismos de toler&#226;ncia imunol&#243;gica em diferentes fases de atividade da doen&#231;a s&#227;o necess&#225;rias para esclarecer o papel da Hsp70 circulante no vitiligo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Em conclus&#227;o&#44; os n&#237;veis plasm&#225;ticos de Hsp70 n&#227;o se correlacionaram diretamente com a extens&#227;o do vitiligo&#59; entretanto&#44; maior positividade foi identificada em participantes com formas regressivas da doen&#231;a&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Aprova&#231;&#227;o pelo Comit&#234; de &#201;tica</span><p id="par0080" class="elsevierStylePara elsevierViewall">Este projeto foi aprovado pelo Comit&#234; de &#201;tica da Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; &#40;parecer n&#250;mero&#160;4&#46;333&#46;389&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">FUNADERM&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">Helena Zenedin Marchioro&#58; Concep&#231;&#227;o do estudo&#59; coleta dos dados&#59; an&#225;lise dos resultados&#59; escrita do texto&#59; revis&#227;o e aprova&#231;&#227;o do texto final&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Caio C&#233;sar Silva de Castro&#58; Concep&#231;&#227;o do estudo&#59; an&#225;lise dos resultados&#59; escrita do texto&#59; revis&#227;o e aprova&#231;&#227;o do texto final&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Isabella Gizzi Jiacomini&#58; Coleta dos dados&#44; an&#225;lise dos resultados&#59; revis&#227;o e aprova&#231;&#227;o final do texto&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do artigo&#59; revis&#227;o cr&#237;tica de 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="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflito de interesses</span><p id="par0110" class="elsevierStylePara elsevierViewall">Helena Zenedin Marchioro&#58; Nenhum&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Caio C&#233;sar Silva de Castro&#58; Ache &#8211; speaker&#44; advisory board&#59; Sun pharma &#8211; advisory board&#59; Abbvie &#8211; advisory board&#59; Pfizer &#8211; clinical trial&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Isabella Gizzi Jiacomini&#58; Nenhum&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Nenhum&#46;</p></span></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>I e II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&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">20&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes <span class="elsevierStyleItalic">mellitus</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">8&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">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a tireoideana&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Depress&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \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">19&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ansiedade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dislipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade de in&#237;cio do vitiligo&#44; mediana &#40;DIQ&#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">38&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">15&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tempo de doen&#231;a &#40;anos&#41;&#44; m&#233;dia &#40;DP&#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">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tratamentos atuais&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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
                  \t\t\t\t</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\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Corticoide t&#243;pico&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">12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#44;5&#37;&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"><span class="elsevierStyleHsp" style=""></span>Inibidor de calcineurina t&#243;pico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \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">47&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PUVA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NB&#8208;UVB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Atividade da doen&#231;a&#44; n &#40;&#37;&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Regress&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Est&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Progress&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&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">69&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">VES&#44; mediana &#40;DIQ&#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">1&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hsp70 &#40;ng&#47;mL&#41;&#44; mediana &#40;DIQ&#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">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hsp70</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#62;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2&#44;8&#160;ng&#47;mL&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&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">43&#37;&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Frequ&#234;ncia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo &#40;masculino&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30 &#40;34&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;40 &#40;0&#44;51&#8208;3&#44;82&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;513&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Idade &#40;&#62; 50 anos&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;23 &#40;0&#44;50&#8208;3&#44;02&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;650&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fototipo</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>I e II&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">1 &#40;&#8722;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40 &#40;45&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;38 &#40;0&#44;42&#8208;4&#44;53&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IV e V&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">27 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;04 &#40;0&#44;60&#8208;6&#44;94&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">VES &#40;&#62; 3&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28 &#40;32&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;36 &#40;0&#44;49&#8208;3&#44;77&#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
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                  \t\t\t\t">0&#44;550&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Atividade da doen&#231;a</span>&nbsp;\t\t\t\t\t\t\n
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                  \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><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;026</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Regress&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Est&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;17 &#40;0&#44;03&#8208;0&#44;94&#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\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Progress&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">62 &#40;39&#37;&#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">0&#44;16 &#40;0&#44;04&#8208;0&#44;69&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Modelo log&#237;stico multivariado da associa&#231;&#227;o entre valores plasm&#225;ticos elevados de Hsp70 &#40;&#62; 2&#44;8&#160;ng&#47;mL&#41; com dados cl&#237;nicos e demogr&#225;ficos de pacientes adultos com vitiligo n&#227;o segmentar &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>89&#41;</p>"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of vitiligo in Brazil&#8208;A population survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;C&#46; Silva de Castro"
                            1 => "H&#46;A&#46; Miot"
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                    0 => array:2 [
                      "doi" => "10.1111/pcmr.12681"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pigment Cell Melanoma Res&#46;"
                        "fecha" => "2018"
                        "volumen" => "31"
                        "paginaInicial" => "448"
                        "paginaFinal" => "450"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29272074"
                            "web" => "Medline"
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                      "titulo" => "Update on the pathogenesis of vitiligo"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46;Z&#46; Marchioro"
                            1 => "C&#46;C&#46;S&#46; Castro"
                            2 => "V&#46;M&#46; Fava"
                            3 => "P&#46;H&#46; Sakiyama"
                            4 => "G&#46; Dellatorre"
                            5 => "H&#46;A&#46; Miot"
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                    0 => array:2 [
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                        "tituloSerie" => "An Bras Dermatol&#46;"
                        "fecha" => "2022"
                        "volumen" => "97"
                        "paginaInicial" => "478"
                        "paginaFinal" => "490"
                        "link" => array:1 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A central role for inducible heat&#8208;shock protein 70 in autoimmune vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;A&#46; Mosenson"
                            1 => "J&#46;M&#46; Eby"
                            2 => "C&#46; Hernandez"
                            3 => "I&#46;C&#46; Le Poole"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1111/exd.12183"
                      "Revista" => array:6 [
                        "tituloSerie" => "Exp Dermatol&#46;"
                        "fecha" => "2013"
                        "volumen" => "22"
                        "paginaInicial" => "566"
                        "paginaFinal" => "569"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23786523"
                            "web" => "Medline"
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                  "contribucion" => array:1 [
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                      "titulo" => "HSP70i is a critical component of the immune response leading to vitiligo"
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                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;A&#46; Mosenson"
                            1 => "A&#46; Zloza"
                            2 => "J&#46; Klarquist"
                            3 => "A&#46;J&#46; Barfuss"
                            4 => "J&#46;A&#46; Guevara-Patino"
                            5 => "I&#46;C&#46; Poole"
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                    0 => array:2 [
                      "doi" => "10.1111/j.1755-148X.2011.00916.x"
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                        "tituloSerie" => "Pigment Cell Melanoma Res&#46;"
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                        "paginaInicial" => "88"
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                          "autores" => array:5 [
                            0 => "C&#46; Jacquemin"
                            1 => "J&#46; Rambert"
                            2 => "S&#46; Guillet"
                            3 => "D&#46; Thiolat"
                            4 => "N&#46; Boukhedouni"
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                      "doi" => "10.1111/bjd.15550"
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                        "tituloSerie" => "Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells&#58; relevance for cutaneous lupus and vitiligo pathogenesis&#46; Br J Dermatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "177"
                        "paginaInicial" => "1367"
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                0 => array:2 [
                  "contribucion" => array:1 [
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ISSN: 26662752
Original language: Portuguese
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