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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">O vitiligo &#233; doen&#231;a adquirida da pigmenta&#231;&#227;o da pele&#46; Sua principal caracter&#237;stica &#233; a perda de melan&#243;citos da epiderme e&#47;ou a perda de sua fun&#231;&#227;o&#46; O vitiligo &#233; queixa bastante comum&#44; com preval&#234;ncia mundial de 0&#44;2&#37;&#8211;1&#44;8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Sua etiologia exata permanece imprecisa&#59; entretanto&#44; sup&#245;e&#8208;se que autoimunidade desempenhe papel fundamental em sua patog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Beta&#8208;defensinas humanas &#40;HBDs&#41; s&#227;o pequenos pept&#237;deos cati&#244;nicos expressos em tecidos epiteliais em todo o corpo&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> Onze HBDs j&#225; foram identificadas&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> A primeira HBD identificada foi a beta&#8208;defensina humana &#40;HBD&#8208;1&#41;&#44; reconhecida em 1995&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> As HBDs ativam as respostas imunes inatas&#44; tendo efeito antimicrobiano &#40;pept&#237;deos antimicrobianos&#41; contra infec&#231;&#245;es&#46; Al&#233;m disso&#44; as defensinas t&#234;m sido associadas ao desenvolvimento&#44; &#224; modula&#231;&#227;o imunol&#243;gica e &#224; fertilidade&#44; bem como &#224; cicatriza&#231;&#227;o de feridas&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o &#224;s suas fun&#231;&#245;es reguladoras imunol&#243;gicas&#44; as defensinas englobam propriedades pr&#243; e anti&#8208;inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> Os efeitos pr&#243;&#8208;inflamat&#243;rios ocorrem por meio da liga&#231;&#227;o com o receptor da defensina&#46; Com base em sua natureza cati&#244;nica&#44; as beta&#8208;defensinas interagem com uma diversidade de receptores que surgem da liga&#231;&#227;o eletrost&#225;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> A fun&#231;&#227;o contradit&#243;ria das beta&#8208;defensinas &#40;como anti&#8208;inflamat&#243;rias&#41; foi demonstrada por meio de sua capacidade de atenuar uma resposta pr&#243;&#8208;inflamat&#243;ria&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O mecanismo pelo qual as beta&#8208;defensinas podem neutralizar a rea&#231;&#227;o pr&#243;&#8208;inflamat&#243;ria n&#227;o est&#225; bem identificado&#44; por&#233;m alguns mecanismos foram considerados&#46; A liga&#231;&#227;o das defensinas &#40;com carga positiva&#41; a ligantes de carga negativa&#44; como os lipopolissacar&#237;deos &#40;LPS&#41;&#44; &#233; mecanismo que possivelmente interfere na liga&#231;&#227;o com o ligante&#46; Ainda&#44; as defensinas podem atuar como antagonistas dos receptores utilizados por provoca&#231;&#245;es pr&#243;&#8208;inflamat&#243;rias&#46; Al&#233;m disso&#44; as beta&#8208;defensinas podem induzir a express&#227;o de alguns mediadores anti&#8208;inflamat&#243;rios&#46; Al&#233;m disso&#44; as defensinas &#40;p&#46; ex&#46;&#44; LL&#8208;37&#41; podem romper as membranas celulares&#44; induzindo efeitos imunossupressores&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A HBD&#8208;1 &#233; um pept&#237;deo de 3928&#44;6 kDa&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> &#201; expressa principalmente no epit&#233;lio e tem papel antimicrobiano contra v&#237;rus e bact&#233;rias gram&#8208;negativas e positivas&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> Al&#233;m dessa fun&#231;&#227;o antimicrobiana ativa&#44; a HBD&#8208;1 tem efeitos imunomoduladores&#44; pois &#233; regulada positivamente em diferentes condi&#231;&#245;es inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> A HBD&#8208;1 &#233; programada pelo gene DEFB1&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> que foi mapeado no cromossomo 8p22&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Tendo em vista a autoimunidade&#44; os polimorfismos dos genes HBD&#8208;1 e DEFB1 foram estudados em algumas doen&#231;as sist&#234;micas e dermatol&#243;gicas com graus vari&#225;veis de associa&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#8211;18</span></a> Entretanto&#44; a associa&#231;&#227;o entre esse polimorfismo g&#234;nico e o vitiligo n&#227;o foi suficientemente estudada em diferentes popula&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Portanto&#44; o objetivo do presente estudo foi elucidar o poss&#237;vel papel da HBD&#8208;1 na patog&#234;nese do VNS por meio da avalia&#231;&#227;o dos n&#237;veis s&#233;ricos de HBD&#8208;1 e seu polimorfismo g&#234;nico em pacientes eg&#237;pcios portadores de VNS&#44; al&#233;m de correlacionar os resultados com os aspectos cl&#237;nicos do vitiligo nesses pacientes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes e m&#233;todos</span><p id="par0040" class="elsevierStylePara elsevierViewall">O presente trabalho &#233; um estudo de caso&#8208;controle e incluiu 50 pacientes com VNS atendidos no Ambulat&#243;rio de Dermatologia da Faculdade de Medicina&#44; Menoufia University&#44; durante o per&#237;odo de dezembro de 2019 a outubro de 2020&#46; O diagn&#243;stico definitivo de vitiligo foi estabelecido com base na apresenta&#231;&#227;o cl&#237;nica t&#237;pica da doen&#231;a por dois dermatologistas especialistas&#46; O grupo controle incluiu 50 pessoas aparentemente saud&#225;veis&#44; pareadas por g&#234;nero e idade&#44; sem hist&#243;rico familiar de vitiligo&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O presente estudo foi aprovado pelo Comit&#234; de &#201;tica em Direitos Humanos em Pesquisa da Faculdade de Medicina&#44; Menoufia University&#44; e estava de acordo com a Declara&#231;&#227;o de Helsinque de 1975 &#40;revisada em 2000&#41;&#46; O estudo tem registro de aprova&#231;&#227;o do comit&#234; de &#233;tica &#40;1202&#47;2&#47;4&#47;20120&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Cada participante recebeu uma explica&#231;&#227;o completa sobre a natureza e o objetivo do estudo&#46; Um termo de consentimento por escrito foi obtido de cada participante ou de seus pais &#40;&#60; 18 anos&#41; antes do in&#237;cio do estudo&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos pacientes com VNS de ambos os sexos&#46; Indiv&#237;duos com qualquer uma das seguintes doen&#231;as foram exclu&#237;dos&#58; 1&#41; doen&#231;as sist&#234;micas &#40;p&#46; ex&#46;&#44; diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; cirrose&#44; infec&#231;&#227;o e insufici&#234;ncia renal&#59; 2&#41; doen&#231;as autoimunes &#40;sist&#234;micas ou cut&#226;neas&#59; p&#46; ex&#46;&#44; artrite reumatoide e psor&#237;ase&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Os casos estudados foram submetidos a anamnese e exame cl&#237;nico&#46; Foi realizado exame dermatol&#243;gico para identificar o tipo de VNS e sua distribui&#231;&#227;o&#46; O escore VASI foi utilizado para determinar a gravidade do vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Foram obtidos 5<span class="elsevierStyleHsp" style=""></span>mL de sangue venoso de cada participante estudado &#40;pacientes e controles&#41;&#46; Desses 5<span class="elsevierStyleHsp" style=""></span>mL&#44; 2<span class="elsevierStyleHsp" style=""></span>mL foram deixados para coagular e depois centrifugados para separar o soro&#46; Os soros separados foram armazenados em recipiente de pl&#225;stico est&#233;ril a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o momento da an&#225;lise dos n&#237;veis s&#233;ricos de HBD&#8208;1&#46; A segunda parte &#40;3<span class="elsevierStyleHsp" style=""></span>mL&#41; foi armazenada a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C em tubos contendo &#225;cido etileno diamina tetra ac&#233;tico &#40;EDTA&#41; para posterior an&#225;lise do polimorfismo do gene da beta&#8208;defensina por an&#225;lise de polimorfismo de fragmentos de restri&#231;&#227;o utilizando a rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#8208;RFLP&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ensaio ELISA para os n&#237;veis s&#233;ricos de beta&#8208;defensina&#8208;1</span><p id="par0070" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de beta&#8208;defensina&#8208;1 foram medidos por kits ELISA &#40;NeoBioscience Technology Co&#46;&#44; Ltd&#44; Shenzhen&#44; Rep&#250;blica Popular da China&#41; de acordo com as instru&#231;&#245;es do fabricante&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Genotipagem para o polimorfismo do gene DEFB1&#8208;20G&#47;A &#40;rs11362&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">A extra&#231;&#227;o do DNA foi feita em uma amostra de sangue utilizando o Mini Kit Gene JET&#174; Whole Blood Genomic DNA Purification &#40;THERMO SCIENTIFIC&#44; EU&#47;Litu&#226;nia&#41;&#44; seguindo as instru&#231;&#245;es do fabricante&#46; O SNP para o gene DEFB1 &#8722;20G&#47;A &#40;rs11362&#41; foi realizado por PCR&#8208;RFLP&#46; As sequ&#234;ncias dos primers foram&#58; F&#58; CTT GAC TGT GGC ACC TCC CTT CAG&#8208;&#40;<span class="elsevierStyleItalic">sense</span>&#41; e R&#58; &#8208;CAG CCC TGG GGA TGG GAA ACT C&#8208; &#40;<span class="elsevierStyleItalic">antisense</span>&#41;&#46; As rea&#231;&#245;es de PCR foram realizadas em um volume total de 30 uL contendo 60 ng de DNA&#44; 3<span class="elsevierStyleHsp" style=""></span>&#956;L 10&#215; PCR Gold Buffer&#44; 2&#44;5<span class="elsevierStyleHsp" style=""></span>mM MgCl2&#44; 200 uM de cada desoxinucleot&#237;deo trifosfato&#44; 0&#44;4<span class="elsevierStyleHsp" style=""></span>mM de cada primer e 1 U de Ampli Taq Gold polimerase&#46; As amostras foram desnaturadas a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 10 minutos&#44; seguido por 30 ciclos de 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos&#44; temperatura de hibridiza&#231;&#227;o de 66<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos e 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos&#44; e uma extens&#227;o final por 10 minutos a 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Ap&#243;s a PCR&#44; os produtos foram digeridos com uma enzima de restri&#231;&#227;o espec&#237;fica&#44; ScrFI &#40;para G&#8208;20A&#41; &#40;Jingmei Biotech&#44; Xangai&#41;&#46; A genotipagem foi realizada &#224;s cegas&#46; O produto de PCR de 268 pb foi digerido por ScrFI durante uma noite a 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0080" class="elsevierStylePara elsevierViewall">Os dados foram avaliados com os programas Statistical Package for Social Sciences &#40;SPSS&#41; vers&#227;o 23 e Epicalc 2000&#46; As estat&#237;sticas foram divididas em duas partes&#58; a&#41; estat&#237;sticas descritivas&#58; ex&#46; m&#233;dia &#40;X<span class="elsevierStyleSup">&#772;</span>&#41;&#44; mediana&#44; desvio padr&#227;o &#40;DP&#41;&#44; intervalo&#44; n&#250;meros &#40;N&#41; e porcentagens &#40;&#37;&#41;&#59; e b&#41; estat&#237;stica anal&#237;tica utilizando o teste do qui&#8208;quadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41;&#44; teste <span class="elsevierStyleItalic">t</span> de Student &#40;t&#41;&#44; teste de Mann&#8208;Whitney &#40;U&#41; e teste de Kruskal&#8208;Wallis&#46; O valor de p foi considerado significante se &#8804; 0&#44;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">Dos 50 pacientes com VNS inclu&#237;dos&#44; 23 &#40;46&#37;&#41; eram do sexo feminino e 27 &#40;54&#37;&#41; do sexo masculino&#44; com idade variando de 7 a 60 anos&#46; N&#227;o houve diferen&#231;as significantes entre os pacientes com vitiligo e os controles em rela&#231;&#227;o &#224; idade &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;335&#41; e g&#234;nero &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;070&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Desses pacientes com VNS&#44; seis casos tinham hist&#243;ria familiar positiva para vitiligo &#40;6&#47;50&#44;12&#37;&#41;&#46; A dura&#231;&#227;o da doen&#231;a variou de tr&#234;s a 120 meses&#46; O escore VASI calculado variou de 0&#44;1 a 10&#46; Em rela&#231;&#227;o ao tipo de vitiligo&#44; 18 &#40;36&#37;&#41; pacientes apresentavam vitiligo acrofacial&#44; dez &#40;20&#37;&#41; pacientes tinham vitiligo generalizado e 22 &#40;44&#37;&#41; pacientes tinham vitiligo em placa &#250;nica focal&#46; Somente quatro casos &#40;8&#37;&#41; apresentavam leucotr&#237;quia e quatro casos &#40;8&#37;&#41; apresentavam acometimento de mucosa &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">N&#237;veis s&#233;ricos de HBD&#8208;1</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de HBD&#8208;1 investigados foram significantemente mais baixos nos pacientes com vitiligo &#40;11&#44;14<span class="elsevierStyleHsp" style=""></span>&#177; 4&#44;72 ng&#47;mL&#41; do que nos controles &#40;46&#44;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;77 ng&#47;mL&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Rela&#231;&#227;o entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e os par&#226;metros estudados de pacientes com vitiligo</span><p id="par0100" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram associados ou correlacionados significantemente com nenhum dos dados pessoais ou cl&#237;nicos dos pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05 para todos&#59; dados n&#227;o apresentados&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lise do equil&#237;brio de Hardy&#8208;Weinberg &#40;EHW&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">A aplica&#231;&#227;o do EHW para os gen&#243;tipos de DEFB&#8208;1 revelou que tanto os casos quanto o grupo controle apresentaram diferen&#231;as n&#227;o significantes entre os valores observados e esperados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;290 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;432 respectivamente&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Distribui&#231;&#227;o de gen&#243;tipos e alelos de DEFB&#8208;1</span><p id="par0110" class="elsevierStylePara elsevierViewall">O estudo do polimorfismo de nucleot&#237;deo &#250;nico de DEFB1 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41; mostrou que houve predom&#237;nio significante do gen&#243;tipo GG em pacientes com vitiligo em 37 &#40;74&#37;&#41; e predom&#237;nio do gen&#243;tipo AA nos controles &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Al&#233;m disso&#44; a presen&#231;a do alelo G foi demonstrada de maneira significante em 87 casos estudados &#40;87&#37;&#41; em rela&#231;&#227;o aos 10 controles &#40;10&#37;&#41;&#44; aumentando o risco de vitiligo em 60 vezes &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#44;23&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Rela&#231;&#227;o entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e seus gen&#243;tipos</span><p id="par0115" class="elsevierStylePara elsevierViewall">O n&#237;vel s&#233;rico de HBD&#8208;1 mostrou associa&#231;&#227;o n&#227;o significante com os gen&#243;tipos de DEFB&#8208;1 em pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;611&#41; e no grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;716&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Rela&#231;&#227;o entre gen&#243;tipos de DEFB&#8208;1 e par&#226;metros pessoais e cl&#237;nicos estudados de pacientes com vitiligo</span><p id="par0120" class="elsevierStylePara elsevierViewall">Os gen&#243;tipos DEFB&#8208;1 mostraram associa&#231;&#227;o n&#227;o significante com os dados pessoais e cl&#237;nicos estudados de pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05 para todos&#59; dados n&#227;o mostrados&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discuss&#227;o</span><p id="par0125" class="elsevierStylePara elsevierViewall">A rea&#231;&#227;o Th17 &#233; descrita pela elicita&#231;&#227;o de AMPs por meio da sinaliza&#231;&#227;o de IL&#8208;17A&#44; IL&#8208;22 e IL&#8208;17F&#44; resultando em inflama&#231;&#227;o localizada&#46; Os AMPs que incluem HBD&#8208;1&#44; s&#227;o capazes de exercer quimioatra&#231;&#227;o de c&#233;lulas dendr&#237;ticas imaturas&#44; c&#233;lulas T e neutr&#243;filos diretamente via sinaliza&#231;&#227;o de CCR6 e indiretamente por meio da indu&#231;&#227;o de HBD&#8208;3&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> Na exist&#234;ncia de sinais de amea&#231;a &#40;como estresse oxidativo e n&#237;veis extraordin&#225;rios de IL&#8208;6&#44; IL&#8208;8&#44; bem como prote&#237;na de choque t&#233;rmico 70&#41;&#44; essa quimioatra&#231;&#227;o pode promover a apresenta&#231;&#227;o de autoant&#237;genos&#44; resultando em despigmenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">23&#44;24</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Portanto&#44; era esperada regula&#231;&#227;o positiva da concentra&#231;&#227;o de HBD&#8208;1 circulante em pacientes com vitiligo em compara&#231;&#227;o com seus pares&#46; No entanto&#44; no presente estudo&#44; foram observados n&#237;veis s&#233;ricos de HBD&#8208;1 significantemente mais baixos em casos de vitiligo em compara&#231;&#227;o aos controles&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Confirmando esse resultado inesperado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> investigaram 171 pacientes mexicanos com VNS&#46; Eles notaram que a HBD&#8208;1 tinha concentra&#231;&#245;es estimadas mais baixas em pacientes com VNS do que nos controles&#46; Al&#233;m disso&#44; os autores descobriram que os casos com vitiligo ativo tinham concentra&#231;&#245;es de HBD&#8208;1 mais baixas do que aqueles com doen&#231;a est&#225;vel&#44; propondo que os n&#237;veis baixos de HBD&#8208;1 circulante estejam ligados &#224; atividade do vitiligo&#46; Al&#233;m disso&#44; no diabetes tipo 1 &#40;DM1&#41;&#44; doen&#231;a mediada por CD8&#43; CTLs&#44; os n&#237;veis circulantes de HBD&#8208;1 foram relatados como significantemente mais baixos do que no grupo controle&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao DM1&#44; um poss&#237;vel esclarecimento para esse resultado &#233; que a ativa&#231;&#227;o extrema do subgrupo de c&#233;lulas T citot&#243;xicas CD8&#43;&#44; caracter&#237;stica do DM1&#44; afeta negativamente a HBD&#8208;1&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> Al&#233;m disso&#44; a sinaliza&#231;&#227;o da insulina &#233; importante para a express&#227;o ideal de HBD&#8208;1 por meio do aumento das concentra&#231;&#245;es intracelulares da glicose e da media&#231;&#227;o da express&#227;o g&#234;nica&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">No entanto&#44; no vitiligo&#44; &#233; sugerido que a subpopula&#231;&#227;o de c&#233;lulas CTL CD8&#43; d&#233;rmicas possa ser respons&#225;vel pela produ&#231;&#227;o local e regula&#231;&#227;o positiva local de HBD&#8208;1 que participa do processo inflamat&#243;rio e despigmenta&#231;&#227;o localizada da pele&#44; sem qualquer efeito sist&#234;mico nos n&#237;veis de HBD&#8208;1&#46; Al&#233;m disso&#44; &#233; sugerido que a HBD&#8208;1 possa ser transferida da corrente sangu&#237;nea para a pele com vitiligo induzindo a despigmenta&#231;&#227;o&#44; e que essa transfer&#234;ncia tenha resultado em seus n&#237;veis s&#233;ricos mais baixos&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Confirmando a presente hip&#243;tese sobre os efeitos inflamat&#243;rios locais da HBD&#8208;1&#44; Polesello et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> e Ozlu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> demonstraram aumento de HBD&#8208;1 na saliva e em bi&#243;psias de pele em pacientes com l&#237;quen plano oral e psor&#237;ase&#44; respectivamente&#46; Portanto&#44; estudos para avaliar simultaneamente os n&#237;veis sist&#234;micos e teciduais de HBD&#8208;1 s&#227;o recomendados&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Outra explica&#231;&#227;o para os baixos n&#237;veis de HBD&#8208;1 demonstrados atualmente em casos de vitiligo pode ser o fato de que a HBD tem fun&#231;&#227;o anti&#8208;inflamat&#243;ria sist&#234;mica&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> Recentemente&#44; foi levantada a hip&#243;tese de que a HBD&#8208;2 poderia suprimir as secre&#231;&#245;es&#44; mediadas por c&#233;lulas dendr&#237;ticas&#44; de citocinas pr&#243;&#8208;inflamat&#243;rias&#44; como IL&#8208;1&#946;&#44; IL&#8208;12 e TNF&#8208;&#945; na doen&#231;a inflamat&#243;ria intestinal &#40;DII&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a> bem como diminuir IL&#8208;6 e TNF&#8208;&#945; em tecidos pulmonares&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; a HBD&#8208;3 reduz a secre&#231;&#227;o de IL&#8208;6 e IL&#8208;8&#44; mostrando potencial promissor como terapia adjuvante para o tratamento de periodontite inflamat&#243;ria&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Assim&#44; &#233; poss&#237;vel que no vitiligo&#44; a HBD&#8208;1 poderia atuar como pept&#237;deo anti&#8208;inflamat&#243;rio&#44; e os baixos n&#237;veis s&#233;ricos de HBD&#8208;1 demonstrados em pacientes com vitiligo podem ser traduzidos em atividade anti&#8208;inflamat&#243;ria reprimida&#46; Portanto&#44; mais estudos sobre a HBD&#8208;1 s&#227;o necess&#225;rios para verificar essa hip&#243;tese&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">No presente estudo&#44; foi observado que os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram afetados por nenhuma caracter&#237;stica pessoal ou cl&#237;nica avaliada nos pacientes com vitiligo&#46; Esse resultado est&#225; de acordo com os de Ochoa&#8208;Ram&#237;rez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> que observaram associa&#231;&#227;o n&#227;o significante entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e as caracter&#237;sticas cl&#237;nicas do vitiligo&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">O gene DEFB1 &#40;localizado no cromossomo 8p22&#41; consiste em dois &#233;xons&#46; O primeiro codifica a pr&#243;&#8208;sequ&#234;ncia e o sinal&#44; ricos em leucina&#46; O segundo &#233;xon&#44; no entanto&#44; codifica o pept&#237;deo maduro&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> Os SNPs desse gene podem ocorrer em diferentes locais das 50 regi&#245;es n&#227;o codificadoras do primeiro &#233;xon&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> incluindo &#8722;52G<span class="elsevierStyleHsp" style=""></span>&#62; A &#40;rs1799946&#41;&#44; &#8722;44C<span class="elsevierStyleHsp" style=""></span>&#62; G &#40;rs1800972&#41; e &#8722;20G<span class="elsevierStyleHsp" style=""></span>&#62; A &#40;rs11362&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">O presente trabalho analisou o polimorfismo dos gen&#243;tipos &#8722;20G&#47;A &#40;rs11362&#41; da DEFB1&#46; Foi observada predomin&#226;ncia significante do gen&#243;tipo GG DEFB1 &#40;&#8722;20G&#47;A&#41; em pacientes com vitiligo em compara&#231;&#227;o com os controles&#44; bem como do alelo G&#44; o que aumentou a possibilidade de ocorr&#234;ncia de vitiligo em cerca de 60 vezes&#46; Entretanto&#44; nos controles foi demonstrado que o gen&#243;tipo DEFB1 &#40;&#8722;20G&#47;A&#41; AA e o alelo A eram significantemente frequentes e considerados de valor protetivo&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Em conson&#226;ncia com esse resultado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram que houve predomin&#226;ncia do gen&#243;tipo GG na posi&#231;&#227;o 20 em pacientes com vitiligo em rela&#231;&#227;o aos controles&#46; Al&#233;m disso&#44; Salem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> estudaram 50 pacientes eg&#237;pcios com VNS e demonstraram que o gen&#243;tipo AA do gene DEFB1 &#40;&#8722;20G&#47;A&#41; e o alelo A tinham frequ&#234;ncias significantemente mais baixas em pacientes com vitiligo e exerciam um efeito protetor contra o desenvolvimento da doen&#231;a&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; na dermatite at&#243;pica &#40;uma doen&#231;a inflamat&#243;ria mediada por c&#233;lulas T&#41;&#44; de Oca et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> descobriram que o gen&#243;tipo &#8722;20 GG representa fator de risco gen&#233;tico para o desenvolvimento de dermatite at&#243;pica&#46; Por outro lado&#44; na DII &#40;doen&#231;a imuno&#8208;inflamat&#243;ria&#41;&#44; Zanin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> relataram que os pacientes com DII apresentavam alelo G mais frequentemente do que os controles&#46; Entretanto&#44; no l&#250;pus eritematoso sist&#234;mico &#40;LES&#41;&#44; que &#233; uma doen&#231;a autoimune&#44; Sandrin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> relataram que o gen&#243;tipo AA e seu alelo A apresentaram frequ&#234;ncias menos significantes no grupo de pacientes em rela&#231;&#227;o ao grupo controle&#44; mostrando efeitos protetores&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Certos polimorfismos do gene da DEFB1 podem afetar a atividade de transcri&#231;&#227;o da DEFB1 e consequentemente a express&#227;o da prote&#237;na HBD&#8208;1&#46; De fato&#44; polimorfismos na regi&#227;o 50 n&#227;o traduzida do gene da DEFB1 alteram o s&#237;tio de liga&#231;&#227;o do fator de transcri&#231;&#227;o putativo para a subunidade p105 do fator nuclear&#8208;KB&#44; resultando na express&#227;o da prote&#237;na HBD1&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">No presente estudo&#44; os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram significantemente afetados pelo SNP do gene da DEFB1&#44; tanto em pacientes com vitiligo quanto no grupo controle&#46; Em apoio a esse resultado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram associa&#231;&#227;o n&#227;o significante entre as concentra&#231;&#245;es s&#233;ricas de HBD&#8208;1 e os gen&#243;tipos de DEFB1&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Entretanto&#44; na DII&#44; Zanin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> relataram que a localiza&#231;&#227;o da doen&#231;a de Crohn col&#244;nica estava ligada &#224; express&#227;o deficiente de HBD&#8208;1&#44; pois o alelo &#40;c&#46;&#8722;20G&#47;A&#41; A parece estar relacionado a n&#237;veis reduzidos de express&#227;o local de HBD&#8208;1&#46; Os autores conclu&#237;ram que o polimorfismo do gene da DEFB1 pode causar menor express&#227;o de HBD&#8208;1 em c&#233;lulas epiteliais do c&#243;lon&#46; O mecanismo patog&#234;nico diferente do vitiligo e da doen&#231;a de Crohn&#44; bem como o tamanho da amostra diferente entre aquele estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>145&#41; e o presente estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#41; podem explicar a diferen&#231;a&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">No presente estudo foi observado que os gen&#243;tipos de DEFB1 n&#227;o tiveram efeitos significantes em nenhuma das caracter&#237;sticas pessoais estudadas ou dados cl&#237;nicos dos pacientes com vitiligo estudados &#40;idade&#44; sexo&#44; dura&#231;&#227;o da doen&#231;a e escore VASI&#41;&#46; Confirmando esse estudo&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram associa&#231;&#227;o n&#227;o significante entre os gen&#243;tipos de DEFB1 e os dados cl&#237;nicos estudados de casos de VNS&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Entretanto&#44; o estudo de Salem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> estava parcialmente de acordo com esses resultados&#46; Eles demonstraram diferen&#231;a n&#227;o significante na distribui&#231;&#227;o dos gen&#243;tipos de DEFB1 &#40;&#8722;20G&#47;A&#41; em rela&#231;&#227;o &#224; hist&#243;ria e achados cl&#237;nicos diferentes&#44; exceto para o escore VASI m&#233;dio&#46; Eles descobriram que os portadores do gen&#243;tipo AA estavam associados a escores VASI significantemente mais baixos&#46; Essa diferen&#231;a pode ser decorrente do pequeno tamanho da amostra em cada estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 pacientes com VNS&#41; e&#47;ou diferentes crit&#233;rios de sele&#231;&#227;o dos casos investigados&#44; pois eles estudaram apenas pacientes com VNS ativo&#44; enquanto o presente estudo avaliou pacientes com VNS independentemente da atividade da doen&#231;a&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">As limita&#231;&#245;es do presente estudo foram a&#41; o pequeno n&#250;mero de casos investigados&#44; b&#41; sua estrutura &#40;estudo de caso controle&#41; e c&#41; avalia&#231;&#227;o de apenas um &#250;nico marcador inflamat&#243;rio em vez de m&#250;ltiplos marcadores&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclus&#245;es</span><p id="par0220" class="elsevierStylePara elsevierViewall">Parece que o polimorfismo do gene da DEFB1 em &#8722;20 pode modular o risco de desenvolvimento de vitiligo&#44; pois o gen&#243;tipo GG DEFB1 &#40;&#8722;20G&#47;A&#41; e o alelo G contribuem para o desenvolvimento de vitiligo em popula&#231;&#245;es eg&#237;pcias&#46; A diminui&#231;&#227;o dos n&#237;veis circulantes de HBD&#8208;1 pode ter papel ativo na etiopatogenia do vitiligo&#44; que pode ser mediada por seus poss&#237;veis efeitos anti&#8208;inflamat&#243;rios&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Suporte financeiro</span><p id="par0225" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Contribui&#231;&#227;o dos autores</span><p id="par0230" class="elsevierStylePara elsevierViewall">Todos os autores devem ter feito contribui&#231;&#245;es substanciais para todos os itens a seguir&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Azza Gaber Antar Farag&#58; Revis&#227;o cr&#237;tica da literatura&#59; concep&#231;&#227;o e planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Mohamed Abd Al Moneam Shoaib&#58; Concep&#231;&#227;o e planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Azza Zagloul labeeb&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Asmaa Shaaban Sleem&#58; Interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Hagar Mahmoud AbdElkader Khallaf&#58; Obten&#231;&#227;o de dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Amany Salah Khalaf&#58; An&#225;lise e interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Mustafa Elsayed Elshaib&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Nada Farag Elnaidany&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Hayam Mohamed Aboelnasr Hanout&#58; Planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflito de interesses</span><p id="par0280" 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">O vitiligo &#233; doen&#231;a adquirida caracterizada por despigmenta&#231;&#227;o da pele&#44; que tem fundo gen&#233;tico e autoimune&#46; A beta&#8208;defensina&#8208;1 humana &#40;HBD&#8208;1&#41; e seu polimorfismo g&#234;nico foram associados a alguns dist&#250;rbios autoimunes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Elucidar o poss&#237;vel papel da HBD&#8208;1 na patog&#234;nese do vitiligo n&#227;o segmentar &#40;VNS&#41; por meio da avalia&#231;&#227;o dos n&#237;veis s&#233;ricos da HBD&#8208;1 e seu polimorfismo de nucleot&#237;deo &#250;nico &#40;SNP&#41; em pacientes com VNS&#44; al&#233;m de correlacionar os resultados com a extens&#227;o do vitiligo nesses pacientes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Um estudo de caso&#8208;controle com inclus&#227;o de 50 pacientes com VNS e 50 controles&#46; O escore <span class="elsevierStyleItalic">Vitiligo Area Scoring Index</span> &#40;VASI&#41; foi utilizado para avaliar a gravidade da doen&#231;a e investiga&#231;&#245;es laboratoriais foram realizadas para avaliar os n&#237;veis s&#233;ricos de HBD&#8208;1 utilizando ELISA e o SNP da defensina&#8208;beta1 &#40;DEFB1&#41; por an&#225;lise de polimorfismo de fragmentos de restri&#231;&#227;o utilizando a rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#8208;RFLP&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de HBD&#8208;1 significantemente mais baixos foram observados nos casos de VNS do que nos controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Houve predomin&#226;ncia significante do gen&#243;tipo GG DEFB1 e do alelo G nos pacientes com VNS em rela&#231;&#227;o aos controles &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Os n&#237;veis s&#233;ricos dos gen&#243;tipos HBD&#8208;1 e DEFB1 n&#227;o foram associados ou correlacionados de maneira significante com nenhum dos par&#226;metros pessoais e cl&#237;nicos dos pacientes com vitiligo&#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">O pequeno tamanho da amostra&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O polimorfismo do gene DEFB1 &#40;gen&#243;tipo GG e alelo G&#41; pode modular o risco de vitiligo e contribuir para o desenvolvimento de vitiligo em popula&#231;&#245;es eg&#237;pcias&#46; A diminui&#231;&#227;o dos n&#237;veis circulantes de HBD&#8208;1 pode ter papel ativo na etiopatogenia do vitiligo&#44; que pode ser mediada por seus poss&#237;veis efeitos anti&#8208;inflamat&#243;rios&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Farag AGA&#44; Shoeib MAA&#44; labeeb AZ&#44; Sleem AS&#44; Khallaf HMA&#44; Khalifa AS&#44; et al&#46; Human beta&#8208;defensin 1 circulating level and gene polymorphism in non&#8208;segmental vitiligo Egyptian patients&#46; An Bras Dermatol&#46; 2023&#59;98&#58;181&#8211;8&#46;</p>"
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          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Imagens de eletroforese em gel de agarose dos produtos de PCR&#58; 268 pb&#46; &#40;B&#41; Imagens de eletroforese em gel de agarose para SNPs de DEFB1 G20A&#44; gen&#243;tipo AA&#58; 268 pb&#44; gen&#243;tipo GG&#58; 143 pb&#44; 125 pb&#44; gen&#243;tipo AG&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;n &#61; 50&#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\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">92&#44;0&nbsp;\t\t\t\t\t\t\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  " align="left" valign="\n
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                  \t\t\t\t">8&#44;0&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">&#8208;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">EHW&#44; Equil&#237;brio de Hardy&#8208;Weinberg&#59; n&#44; n&#250;mero&#59; DEFB1&#44; gene da defensina humana&#8208;1&#46;</p>"
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                  \t\t\t\t">0&#44;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">40&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">40&#44;5&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">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t">0&#44;290</td><td class="td" title="\n
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Equil&#237;brio de Hardy&#8208;Weinberg para gen&#243;tipos DEFB&#8208;1 de pacientes com vitiligo e grupo controle</p>"
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                  \t\t\t\t" scope="col">&#967;<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">p&#8208;valor&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" scope="col">OR &#40;IC95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">GG&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 &#40;74&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#40;n</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">100&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#40;n</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">100&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">118&#44;69</td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="3" align="left" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001<span class="elsevierStyleSup">a</span></td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="3" align="left" 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">G&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">A&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o percentual de gen&#243;tipos e alelos de DEFB&#8208;1 em pacientes com vitiligo e grupo controle</p>"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">HBD&#8208;1&#44; beta&#8208;defensina humana&#8208;1&#59; n&#44; n&#250;mero&#59; DEFB&#8208;1&#44; gene da defensina humana&#8208;1&#46;</p>"
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                  \t\t\t\t">46&#44;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Teste de Mann&#8208;Whitney&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">N&#237;vel s&#233;rico de HBD&#8208;1 em rela&#231;&#227;o aos gen&#243;tipos de beta&#8208;defensina humana&#8208;1 em pacientes com vitiligo e grupo controle</p>"
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            0 => array:3 [
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                    0 => array:2 [
                      "titulo" => "The enigma and challenges of vitiligo pathophysiology and treatment"
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                          "autores" => array:6 [
                            0 => "Z&#46;A&#46; Abdel-Malek"
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                            2 => "T&#46; Ho"
                            3 => "P&#46;R&#46; Upadhyay"
                            4 => "A&#46; Fleischer"
                            5 => "I&#46; Hamzavi"
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                    0 => array:2 [
                      "doi" => "10.1111/pcmr.12878"
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                        "tituloSerie" => "Pigment Cell Melanoma Res&#46;"
                        "fecha" => "2020"
                        "volumen" => "33"
                        "paginaInicial" => "778"
                        "paginaFinal" => "787"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32198977"
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              "identificador" => "bib0175"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emerging role of immune cell network in autoimmune skin disorders&#58; an update on pemphigus&#44; vitiligo&#44; and psoriasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Das"
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                            2 => "S&#46; Kurra"
                            3 => "S&#46; Gupta"
                            4 => "A&#46; Sharma"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cytogfr.2019.01.001"
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                        "tituloSerie" => "Cytokine Growth Factor Rev&#46;"
                        "fecha" => "2019"
                        "volumen" => "45"
                        "paginaInicial" => "35"
                        "paginaFinal" => "44"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30773437"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial peptides&#8208;promising alternatives to conventional antibiotics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;A&#46; Baltzer"
                            1 => "M&#46;H&#46; Brown"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000331009"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Mol Microbiol Biotechnol&#46;"
                        "fecha" => "2011"
                        "volumen" => "20"
                        "paginaInicial" => "228"
                        "paginaFinal" => "235"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21894027"
                            "web" => "Medline"
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                      "titulo" => "Defensins&#58; natural component of human innate immunity"
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                          "autores" => array:6 [
                            0 => "J&#46; Jarczak"
                            1 => "E&#46;M&#46; Ko&#347;ciuczuk"
                            2 => "P&#46; Lisowski"
                            3 => "N&#46; Strza&#322;kowska"
                            4 => "A&#46; J&#243;&#378;wik"
                            5 => "J&#46; Horba&#324;czuk"
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Artigo original
Níveis circulantes de beta‐defensina humana‐1 e polimorfismo gênico em pacientes egípcios com vitiligo não segmentar
Azza Gaber Antar Faraga,
Autor para correspondência
azzagaber92@yahoo.com

Autor para correspondência.
, Mohamed Abd AlMoneam Shoeiba, Azza Zagloul labeebb, Asmaa Shaaban Sleemb, Hagar Mahmoud AbdElkader Khallafc, Amany Salah Khalifad, Mustafa Elsayed Elshaibe, Nada Farag Elnaidanyf, Hayam Mohamed Aboelnasr Hanouta
a Departamento de Dermatologia, Andrologia e ISTs, Faculdade de Medicina, Menoufia University, Egito
b Departamento de Microbiologia e Imunologia, Faculdade de Medicina, Menoufia University, Egito
c Departamento de Dermatologia, Tala Central Hospital, Ministry of Health, Al‐Menoufia, Egito
d Departamento de Patologia Clínica, Faculdade de Medicina, Menoufia University, Egito
e Acadêmico de Medicina, Faculdade de Medicina, Menoufia University, Egito
f Departamento de Farmácia Clínica, Faculdade de Farmácia, MSA University, Egito
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s&#227;o pequenos pept&#237;deos cati&#244;nicos expressos em tecidos epiteliais em todo o corpo&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> Onze HBDs j&#225; foram identificadas&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> A primeira HBD identificada foi a beta&#8208;defensina humana &#40;HBD&#8208;1&#41;&#44; reconhecida em 1995&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> As HBDs ativam as respostas imunes inatas&#44; tendo efeito antimicrobiano &#40;pept&#237;deos antimicrobianos&#41; contra infec&#231;&#245;es&#46; Al&#233;m disso&#44; as defensinas t&#234;m sido associadas ao desenvolvimento&#44; &#224; modula&#231;&#227;o imunol&#243;gica e &#224; fertilidade&#44; bem como &#224; cicatriza&#231;&#227;o de feridas&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o &#224;s suas fun&#231;&#245;es reguladoras imunol&#243;gicas&#44; as defensinas englobam propriedades pr&#243; e anti&#8208;inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> Os efeitos pr&#243;&#8208;inflamat&#243;rios ocorrem por meio da liga&#231;&#227;o com o receptor da defensina&#46; Com base em sua natureza cati&#244;nica&#44; as beta&#8208;defensinas interagem com uma diversidade de receptores que surgem da liga&#231;&#227;o eletrost&#225;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> A fun&#231;&#227;o contradit&#243;ria das beta&#8208;defensinas &#40;como anti&#8208;inflamat&#243;rias&#41; foi demonstrada por meio de sua capacidade de atenuar uma resposta pr&#243;&#8208;inflamat&#243;ria&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O mecanismo pelo qual as beta&#8208;defensinas podem neutralizar a rea&#231;&#227;o pr&#243;&#8208;inflamat&#243;ria n&#227;o est&#225; bem identificado&#44; por&#233;m alguns mecanismos foram considerados&#46; A liga&#231;&#227;o das defensinas &#40;com carga positiva&#41; a ligantes de carga negativa&#44; como os lipopolissacar&#237;deos &#40;LPS&#41;&#44; &#233; mecanismo que possivelmente interfere na liga&#231;&#227;o com o ligante&#46; Ainda&#44; as defensinas podem atuar como antagonistas dos receptores utilizados por provoca&#231;&#245;es pr&#243;&#8208;inflamat&#243;rias&#46; Al&#233;m disso&#44; as beta&#8208;defensinas podem induzir a express&#227;o de alguns mediadores anti&#8208;inflamat&#243;rios&#46; Al&#233;m disso&#44; as defensinas &#40;p&#46; ex&#46;&#44; LL&#8208;37&#41; podem romper as membranas celulares&#44; induzindo efeitos imunossupressores&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A HBD&#8208;1 &#233; um pept&#237;deo de 3928&#44;6 kDa&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> &#201; expressa principalmente no epit&#233;lio e tem papel antimicrobiano contra v&#237;rus e bact&#233;rias gram&#8208;negativas e positivas&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> Al&#233;m dessa fun&#231;&#227;o antimicrobiana ativa&#44; a HBD&#8208;1 tem efeitos imunomoduladores&#44; pois &#233; regulada positivamente em diferentes condi&#231;&#245;es inflamat&#243;rias&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> A HBD&#8208;1 &#233; programada pelo gene DEFB1&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> que foi mapeado no cromossomo 8p22&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Tendo em vista a autoimunidade&#44; os polimorfismos dos genes HBD&#8208;1 e DEFB1 foram estudados em algumas doen&#231;as sist&#234;micas e dermatol&#243;gicas com graus vari&#225;veis de associa&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15&#8211;18</span></a> Entretanto&#44; a associa&#231;&#227;o entre esse polimorfismo g&#234;nico e o vitiligo n&#227;o foi suficientemente estudada em diferentes popula&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Portanto&#44; o objetivo do presente estudo foi elucidar o poss&#237;vel papel da HBD&#8208;1 na patog&#234;nese do VNS por meio da avalia&#231;&#227;o dos n&#237;veis s&#233;ricos de HBD&#8208;1 e seu polimorfismo g&#234;nico em pacientes eg&#237;pcios portadores de VNS&#44; al&#233;m de correlacionar os resultados com os aspectos cl&#237;nicos do vitiligo nesses pacientes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes e m&#233;todos</span><p id="par0040" class="elsevierStylePara elsevierViewall">O presente trabalho &#233; um estudo de caso&#8208;controle e incluiu 50 pacientes com VNS atendidos no Ambulat&#243;rio de Dermatologia da Faculdade de Medicina&#44; Menoufia University&#44; durante o per&#237;odo de dezembro de 2019 a outubro de 2020&#46; O diagn&#243;stico definitivo de vitiligo foi estabelecido com base na apresenta&#231;&#227;o cl&#237;nica t&#237;pica da doen&#231;a por dois dermatologistas especialistas&#46; O grupo controle incluiu 50 pessoas aparentemente saud&#225;veis&#44; pareadas por g&#234;nero e idade&#44; sem hist&#243;rico familiar de vitiligo&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O presente estudo foi aprovado pelo Comit&#234; de &#201;tica em Direitos Humanos em Pesquisa da Faculdade de Medicina&#44; Menoufia University&#44; e estava de acordo com a Declara&#231;&#227;o de Helsinque de 1975 &#40;revisada em 2000&#41;&#46; O estudo tem registro de aprova&#231;&#227;o do comit&#234; de &#233;tica &#40;1202&#47;2&#47;4&#47;20120&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Cada participante recebeu uma explica&#231;&#227;o completa sobre a natureza e o objetivo do estudo&#46; Um termo de consentimento por escrito foi obtido de cada participante ou de seus pais &#40;&#60; 18 anos&#41; antes do in&#237;cio do estudo&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos pacientes com VNS de ambos os sexos&#46; Indiv&#237;duos com qualquer uma das seguintes doen&#231;as foram exclu&#237;dos&#58; 1&#41; doen&#231;as sist&#234;micas &#40;p&#46; ex&#46;&#44; diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; cirrose&#44; infec&#231;&#227;o e insufici&#234;ncia renal&#59; 2&#41; doen&#231;as autoimunes &#40;sist&#234;micas ou cut&#226;neas&#59; p&#46; ex&#46;&#44; artrite reumatoide e psor&#237;ase&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Os casos estudados foram submetidos a anamnese e exame cl&#237;nico&#46; Foi realizado exame dermatol&#243;gico para identificar o tipo de VNS e sua distribui&#231;&#227;o&#46; O escore VASI foi utilizado para determinar a gravidade do vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Foram obtidos 5<span class="elsevierStyleHsp" style=""></span>mL de sangue venoso de cada participante estudado &#40;pacientes e controles&#41;&#46; Desses 5<span class="elsevierStyleHsp" style=""></span>mL&#44; 2<span class="elsevierStyleHsp" style=""></span>mL foram deixados para coagular e depois centrifugados para separar o soro&#46; Os soros separados foram armazenados em recipiente de pl&#225;stico est&#233;ril a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o momento da an&#225;lise dos n&#237;veis s&#233;ricos de HBD&#8208;1&#46; A segunda parte &#40;3<span class="elsevierStyleHsp" style=""></span>mL&#41; foi armazenada a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C em tubos contendo &#225;cido etileno diamina tetra ac&#233;tico &#40;EDTA&#41; para posterior an&#225;lise do polimorfismo do gene da beta&#8208;defensina por an&#225;lise de polimorfismo de fragmentos de restri&#231;&#227;o utilizando a rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#8208;RFLP&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ensaio ELISA para os n&#237;veis s&#233;ricos de beta&#8208;defensina&#8208;1</span><p id="par0070" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de beta&#8208;defensina&#8208;1 foram medidos por kits ELISA &#40;NeoBioscience Technology Co&#46;&#44; Ltd&#44; Shenzhen&#44; Rep&#250;blica Popular da China&#41; de acordo com as instru&#231;&#245;es do fabricante&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Genotipagem para o polimorfismo do gene DEFB1&#8208;20G&#47;A &#40;rs11362&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">A extra&#231;&#227;o do DNA foi feita em uma amostra de sangue utilizando o Mini Kit Gene JET&#174; Whole Blood Genomic DNA Purification &#40;THERMO SCIENTIFIC&#44; EU&#47;Litu&#226;nia&#41;&#44; seguindo as instru&#231;&#245;es do fabricante&#46; O SNP para o gene DEFB1 &#8722;20G&#47;A &#40;rs11362&#41; foi realizado por PCR&#8208;RFLP&#46; As sequ&#234;ncias dos primers foram&#58; F&#58; CTT GAC TGT GGC ACC TCC CTT CAG&#8208;&#40;<span class="elsevierStyleItalic">sense</span>&#41; e R&#58; &#8208;CAG CCC TGG GGA TGG GAA ACT C&#8208; &#40;<span class="elsevierStyleItalic">antisense</span>&#41;&#46; As rea&#231;&#245;es de PCR foram realizadas em um volume total de 30 uL contendo 60 ng de DNA&#44; 3<span class="elsevierStyleHsp" style=""></span>&#956;L 10&#215; PCR Gold Buffer&#44; 2&#44;5<span class="elsevierStyleHsp" style=""></span>mM MgCl2&#44; 200 uM de cada desoxinucleot&#237;deo trifosfato&#44; 0&#44;4<span class="elsevierStyleHsp" style=""></span>mM de cada primer e 1 U de Ampli Taq Gold polimerase&#46; As amostras foram desnaturadas a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 10 minutos&#44; seguido por 30 ciclos de 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos&#44; temperatura de hibridiza&#231;&#227;o de 66<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos e 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 60 segundos&#44; e uma extens&#227;o final por 10 minutos a 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Ap&#243;s a PCR&#44; os produtos foram digeridos com uma enzima de restri&#231;&#227;o espec&#237;fica&#44; ScrFI &#40;para G&#8208;20A&#41; &#40;Jingmei Biotech&#44; Xangai&#41;&#46; A genotipagem foi realizada &#224;s cegas&#46; O produto de PCR de 268 pb foi digerido por ScrFI durante uma noite a 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0080" class="elsevierStylePara elsevierViewall">Os dados foram avaliados com os programas Statistical Package for Social Sciences &#40;SPSS&#41; vers&#227;o 23 e Epicalc 2000&#46; As estat&#237;sticas foram divididas em duas partes&#58; a&#41; estat&#237;sticas descritivas&#58; ex&#46; m&#233;dia &#40;X<span class="elsevierStyleSup">&#772;</span>&#41;&#44; mediana&#44; desvio padr&#227;o &#40;DP&#41;&#44; intervalo&#44; n&#250;meros &#40;N&#41; e porcentagens &#40;&#37;&#41;&#59; e b&#41; estat&#237;stica anal&#237;tica utilizando o teste do qui&#8208;quadrado &#40;&#967;<span class="elsevierStyleSup">2</span>&#41;&#44; teste <span class="elsevierStyleItalic">t</span> de Student &#40;t&#41;&#44; teste de Mann&#8208;Whitney &#40;U&#41; e teste de Kruskal&#8208;Wallis&#46; O valor de p foi considerado significante se &#8804; 0&#44;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">Dos 50 pacientes com VNS inclu&#237;dos&#44; 23 &#40;46&#37;&#41; eram do sexo feminino e 27 &#40;54&#37;&#41; do sexo masculino&#44; com idade variando de 7 a 60 anos&#46; N&#227;o houve diferen&#231;as significantes entre os pacientes com vitiligo e os controles em rela&#231;&#227;o &#224; idade &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;335&#41; e g&#234;nero &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;070&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Desses pacientes com VNS&#44; seis casos tinham hist&#243;ria familiar positiva para vitiligo &#40;6&#47;50&#44;12&#37;&#41;&#46; A dura&#231;&#227;o da doen&#231;a variou de tr&#234;s a 120 meses&#46; O escore VASI calculado variou de 0&#44;1 a 10&#46; Em rela&#231;&#227;o ao tipo de vitiligo&#44; 18 &#40;36&#37;&#41; pacientes apresentavam vitiligo acrofacial&#44; dez &#40;20&#37;&#41; pacientes tinham vitiligo generalizado e 22 &#40;44&#37;&#41; pacientes tinham vitiligo em placa &#250;nica focal&#46; Somente quatro casos &#40;8&#37;&#41; apresentavam leucotr&#237;quia e quatro casos &#40;8&#37;&#41; apresentavam acometimento de mucosa &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">N&#237;veis s&#233;ricos de HBD&#8208;1</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de HBD&#8208;1 investigados foram significantemente mais baixos nos pacientes com vitiligo &#40;11&#44;14<span class="elsevierStyleHsp" style=""></span>&#177; 4&#44;72 ng&#47;mL&#41; do que nos controles &#40;46&#44;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;77 ng&#47;mL&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Rela&#231;&#227;o entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e os par&#226;metros estudados de pacientes com vitiligo</span><p id="par0100" class="elsevierStylePara elsevierViewall">Os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram associados ou correlacionados significantemente com nenhum dos dados pessoais ou cl&#237;nicos dos pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05 para todos&#59; dados n&#227;o apresentados&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lise do equil&#237;brio de Hardy&#8208;Weinberg &#40;EHW&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">A aplica&#231;&#227;o do EHW para os gen&#243;tipos de DEFB&#8208;1 revelou que tanto os casos quanto o grupo controle apresentaram diferen&#231;as n&#227;o significantes entre os valores observados e esperados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;290 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;432 respectivamente&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Distribui&#231;&#227;o de gen&#243;tipos e alelos de DEFB&#8208;1</span><p id="par0110" class="elsevierStylePara elsevierViewall">O estudo do polimorfismo de nucleot&#237;deo &#250;nico de DEFB1 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41; mostrou que houve predom&#237;nio significante do gen&#243;tipo GG em pacientes com vitiligo em 37 &#40;74&#37;&#41; e predom&#237;nio do gen&#243;tipo AA nos controles &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Al&#233;m disso&#44; a presen&#231;a do alelo G foi demonstrada de maneira significante em 87 casos estudados &#40;87&#37;&#41; em rela&#231;&#227;o aos 10 controles &#40;10&#37;&#41;&#44; aumentando o risco de vitiligo em 60 vezes &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#44;23&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Rela&#231;&#227;o entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e seus gen&#243;tipos</span><p id="par0115" class="elsevierStylePara elsevierViewall">O n&#237;vel s&#233;rico de HBD&#8208;1 mostrou associa&#231;&#227;o n&#227;o significante com os gen&#243;tipos de DEFB&#8208;1 em pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;611&#41; e no grupo controle &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;716&#41; &#8211; <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Rela&#231;&#227;o entre gen&#243;tipos de DEFB&#8208;1 e par&#226;metros pessoais e cl&#237;nicos estudados de pacientes com vitiligo</span><p id="par0120" class="elsevierStylePara elsevierViewall">Os gen&#243;tipos DEFB&#8208;1 mostraram associa&#231;&#227;o n&#227;o significante com os dados pessoais e cl&#237;nicos estudados de pacientes com vitiligo &#40;p<span class="elsevierStyleHsp" style=""></span>&#62; 0&#44;05 para todos&#59; dados n&#227;o mostrados&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discuss&#227;o</span><p id="par0125" class="elsevierStylePara elsevierViewall">A rea&#231;&#227;o Th17 &#233; descrita pela elicita&#231;&#227;o de AMPs por meio da sinaliza&#231;&#227;o de IL&#8208;17A&#44; IL&#8208;22 e IL&#8208;17F&#44; resultando em inflama&#231;&#227;o localizada&#46; Os AMPs que incluem HBD&#8208;1&#44; s&#227;o capazes de exercer quimioatra&#231;&#227;o de c&#233;lulas dendr&#237;ticas imaturas&#44; c&#233;lulas T e neutr&#243;filos diretamente via sinaliza&#231;&#227;o de CCR6 e indiretamente por meio da indu&#231;&#227;o de HBD&#8208;3&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> Na exist&#234;ncia de sinais de amea&#231;a &#40;como estresse oxidativo e n&#237;veis extraordin&#225;rios de IL&#8208;6&#44; IL&#8208;8&#44; bem como prote&#237;na de choque t&#233;rmico 70&#41;&#44; essa quimioatra&#231;&#227;o pode promover a apresenta&#231;&#227;o de autoant&#237;genos&#44; resultando em despigmenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">23&#44;24</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Portanto&#44; era esperada regula&#231;&#227;o positiva da concentra&#231;&#227;o de HBD&#8208;1 circulante em pacientes com vitiligo em compara&#231;&#227;o com seus pares&#46; No entanto&#44; no presente estudo&#44; foram observados n&#237;veis s&#233;ricos de HBD&#8208;1 significantemente mais baixos em casos de vitiligo em compara&#231;&#227;o aos controles&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Confirmando esse resultado inesperado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> investigaram 171 pacientes mexicanos com VNS&#46; Eles notaram que a HBD&#8208;1 tinha concentra&#231;&#245;es estimadas mais baixas em pacientes com VNS do que nos controles&#46; Al&#233;m disso&#44; os autores descobriram que os casos com vitiligo ativo tinham concentra&#231;&#245;es de HBD&#8208;1 mais baixas do que aqueles com doen&#231;a est&#225;vel&#44; propondo que os n&#237;veis baixos de HBD&#8208;1 circulante estejam ligados &#224; atividade do vitiligo&#46; Al&#233;m disso&#44; no diabetes tipo 1 &#40;DM1&#41;&#44; doen&#231;a mediada por CD8&#43; CTLs&#44; os n&#237;veis circulantes de HBD&#8208;1 foram relatados como significantemente mais baixos do que no grupo controle&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao DM1&#44; um poss&#237;vel esclarecimento para esse resultado &#233; que a ativa&#231;&#227;o extrema do subgrupo de c&#233;lulas T citot&#243;xicas CD8&#43;&#44; caracter&#237;stica do DM1&#44; afeta negativamente a HBD&#8208;1&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> Al&#233;m disso&#44; a sinaliza&#231;&#227;o da insulina &#233; importante para a express&#227;o ideal de HBD&#8208;1 por meio do aumento das concentra&#231;&#245;es intracelulares da glicose e da media&#231;&#227;o da express&#227;o g&#234;nica&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">No entanto&#44; no vitiligo&#44; &#233; sugerido que a subpopula&#231;&#227;o de c&#233;lulas CTL CD8&#43; d&#233;rmicas possa ser respons&#225;vel pela produ&#231;&#227;o local e regula&#231;&#227;o positiva local de HBD&#8208;1 que participa do processo inflamat&#243;rio e despigmenta&#231;&#227;o localizada da pele&#44; sem qualquer efeito sist&#234;mico nos n&#237;veis de HBD&#8208;1&#46; Al&#233;m disso&#44; &#233; sugerido que a HBD&#8208;1 possa ser transferida da corrente sangu&#237;nea para a pele com vitiligo induzindo a despigmenta&#231;&#227;o&#44; e que essa transfer&#234;ncia tenha resultado em seus n&#237;veis s&#233;ricos mais baixos&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Confirmando a presente hip&#243;tese sobre os efeitos inflamat&#243;rios locais da HBD&#8208;1&#44; Polesello et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> e Ozlu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> demonstraram aumento de HBD&#8208;1 na saliva e em bi&#243;psias de pele em pacientes com l&#237;quen plano oral e psor&#237;ase&#44; respectivamente&#46; Portanto&#44; estudos para avaliar simultaneamente os n&#237;veis sist&#234;micos e teciduais de HBD&#8208;1 s&#227;o recomendados&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Outra explica&#231;&#227;o para os baixos n&#237;veis de HBD&#8208;1 demonstrados atualmente em casos de vitiligo pode ser o fato de que a HBD tem fun&#231;&#227;o anti&#8208;inflamat&#243;ria sist&#234;mica&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> Recentemente&#44; foi levantada a hip&#243;tese de que a HBD&#8208;2 poderia suprimir as secre&#231;&#245;es&#44; mediadas por c&#233;lulas dendr&#237;ticas&#44; de citocinas pr&#243;&#8208;inflamat&#243;rias&#44; como IL&#8208;1&#946;&#44; IL&#8208;12 e TNF&#8208;&#945; na doen&#231;a inflamat&#243;ria intestinal &#40;DII&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a> bem como diminuir IL&#8208;6 e TNF&#8208;&#945; em tecidos pulmonares&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; a HBD&#8208;3 reduz a secre&#231;&#227;o de IL&#8208;6 e IL&#8208;8&#44; mostrando potencial promissor como terapia adjuvante para o tratamento de periodontite inflamat&#243;ria&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Assim&#44; &#233; poss&#237;vel que no vitiligo&#44; a HBD&#8208;1 poderia atuar como pept&#237;deo anti&#8208;inflamat&#243;rio&#44; e os baixos n&#237;veis s&#233;ricos de HBD&#8208;1 demonstrados em pacientes com vitiligo podem ser traduzidos em atividade anti&#8208;inflamat&#243;ria reprimida&#46; Portanto&#44; mais estudos sobre a HBD&#8208;1 s&#227;o necess&#225;rios para verificar essa hip&#243;tese&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">No presente estudo&#44; foi observado que os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram afetados por nenhuma caracter&#237;stica pessoal ou cl&#237;nica avaliada nos pacientes com vitiligo&#46; Esse resultado est&#225; de acordo com os de Ochoa&#8208;Ram&#237;rez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> que observaram associa&#231;&#227;o n&#227;o significante entre os n&#237;veis s&#233;ricos de HBD&#8208;1 e as caracter&#237;sticas cl&#237;nicas do vitiligo&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">O gene DEFB1 &#40;localizado no cromossomo 8p22&#41; consiste em dois &#233;xons&#46; O primeiro codifica a pr&#243;&#8208;sequ&#234;ncia e o sinal&#44; ricos em leucina&#46; O segundo &#233;xon&#44; no entanto&#44; codifica o pept&#237;deo maduro&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> Os SNPs desse gene podem ocorrer em diferentes locais das 50 regi&#245;es n&#227;o codificadoras do primeiro &#233;xon&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> incluindo &#8722;52G<span class="elsevierStyleHsp" style=""></span>&#62; A &#40;rs1799946&#41;&#44; &#8722;44C<span class="elsevierStyleHsp" style=""></span>&#62; G &#40;rs1800972&#41; e &#8722;20G<span class="elsevierStyleHsp" style=""></span>&#62; A &#40;rs11362&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">O presente trabalho analisou o polimorfismo dos gen&#243;tipos &#8722;20G&#47;A &#40;rs11362&#41; da DEFB1&#46; Foi observada predomin&#226;ncia significante do gen&#243;tipo GG DEFB1 &#40;&#8722;20G&#47;A&#41; em pacientes com vitiligo em compara&#231;&#227;o com os controles&#44; bem como do alelo G&#44; o que aumentou a possibilidade de ocorr&#234;ncia de vitiligo em cerca de 60 vezes&#46; Entretanto&#44; nos controles foi demonstrado que o gen&#243;tipo DEFB1 &#40;&#8722;20G&#47;A&#41; AA e o alelo A eram significantemente frequentes e considerados de valor protetivo&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Em conson&#226;ncia com esse resultado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram que houve predomin&#226;ncia do gen&#243;tipo GG na posi&#231;&#227;o 20 em pacientes com vitiligo em rela&#231;&#227;o aos controles&#46; Al&#233;m disso&#44; Salem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> estudaram 50 pacientes eg&#237;pcios com VNS e demonstraram que o gen&#243;tipo AA do gene DEFB1 &#40;&#8722;20G&#47;A&#41; e o alelo A tinham frequ&#234;ncias significantemente mais baixas em pacientes com vitiligo e exerciam um efeito protetor contra o desenvolvimento da doen&#231;a&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; na dermatite at&#243;pica &#40;uma doen&#231;a inflamat&#243;ria mediada por c&#233;lulas T&#41;&#44; de Oca et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> descobriram que o gen&#243;tipo &#8722;20 GG representa fator de risco gen&#233;tico para o desenvolvimento de dermatite at&#243;pica&#46; Por outro lado&#44; na DII &#40;doen&#231;a imuno&#8208;inflamat&#243;ria&#41;&#44; Zanin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> relataram que os pacientes com DII apresentavam alelo G mais frequentemente do que os controles&#46; Entretanto&#44; no l&#250;pus eritematoso sist&#234;mico &#40;LES&#41;&#44; que &#233; uma doen&#231;a autoimune&#44; Sandrin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> relataram que o gen&#243;tipo AA e seu alelo A apresentaram frequ&#234;ncias menos significantes no grupo de pacientes em rela&#231;&#227;o ao grupo controle&#44; mostrando efeitos protetores&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Certos polimorfismos do gene da DEFB1 podem afetar a atividade de transcri&#231;&#227;o da DEFB1 e consequentemente a express&#227;o da prote&#237;na HBD&#8208;1&#46; De fato&#44; polimorfismos na regi&#227;o 50 n&#227;o traduzida do gene da DEFB1 alteram o s&#237;tio de liga&#231;&#227;o do fator de transcri&#231;&#227;o putativo para a subunidade p105 do fator nuclear&#8208;KB&#44; resultando na express&#227;o da prote&#237;na HBD1&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">No presente estudo&#44; os n&#237;veis s&#233;ricos de HBD&#8208;1 n&#227;o foram significantemente afetados pelo SNP do gene da DEFB1&#44; tanto em pacientes com vitiligo quanto no grupo controle&#46; Em apoio a esse resultado&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram associa&#231;&#227;o n&#227;o significante entre as concentra&#231;&#245;es s&#233;ricas de HBD&#8208;1 e os gen&#243;tipos de DEFB1&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Entretanto&#44; na DII&#44; Zanin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> relataram que a localiza&#231;&#227;o da doen&#231;a de Crohn col&#244;nica estava ligada &#224; express&#227;o deficiente de HBD&#8208;1&#44; pois o alelo &#40;c&#46;&#8722;20G&#47;A&#41; A parece estar relacionado a n&#237;veis reduzidos de express&#227;o local de HBD&#8208;1&#46; Os autores conclu&#237;ram que o polimorfismo do gene da DEFB1 pode causar menor express&#227;o de HBD&#8208;1 em c&#233;lulas epiteliais do c&#243;lon&#46; O mecanismo patog&#234;nico diferente do vitiligo e da doen&#231;a de Crohn&#44; bem como o tamanho da amostra diferente entre aquele estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>145&#41; e o presente estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#41; podem explicar a diferen&#231;a&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">No presente estudo foi observado que os gen&#243;tipos de DEFB1 n&#227;o tiveram efeitos significantes em nenhuma das caracter&#237;sticas pessoais estudadas ou dados cl&#237;nicos dos pacientes com vitiligo estudados &#40;idade&#44; sexo&#44; dura&#231;&#227;o da doen&#231;a e escore VASI&#41;&#46; Confirmando esse estudo&#44; Ochoa&#8208;Ram&#237;rez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> observaram associa&#231;&#227;o n&#227;o significante entre os gen&#243;tipos de DEFB1 e os dados cl&#237;nicos estudados de casos de VNS&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Entretanto&#44; o estudo de Salem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> estava parcialmente de acordo com esses resultados&#46; Eles demonstraram diferen&#231;a n&#227;o significante na distribui&#231;&#227;o dos gen&#243;tipos de DEFB1 &#40;&#8722;20G&#47;A&#41; em rela&#231;&#227;o &#224; hist&#243;ria e achados cl&#237;nicos diferentes&#44; exceto para o escore VASI m&#233;dio&#46; Eles descobriram que os portadores do gen&#243;tipo AA estavam associados a escores VASI significantemente mais baixos&#46; Essa diferen&#231;a pode ser decorrente do pequeno tamanho da amostra em cada estudo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 pacientes com VNS&#41; e&#47;ou diferentes crit&#233;rios de sele&#231;&#227;o dos casos investigados&#44; pois eles estudaram apenas pacientes com VNS ativo&#44; enquanto o presente estudo avaliou pacientes com VNS independentemente da atividade da doen&#231;a&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">As limita&#231;&#245;es do presente estudo foram a&#41; o pequeno n&#250;mero de casos investigados&#44; b&#41; sua estrutura &#40;estudo de caso controle&#41; e c&#41; avalia&#231;&#227;o de apenas um &#250;nico marcador inflamat&#243;rio em vez de m&#250;ltiplos marcadores&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclus&#245;es</span><p id="par0220" class="elsevierStylePara elsevierViewall">Parece que o polimorfismo do gene da DEFB1 em &#8722;20 pode modular o risco de desenvolvimento de vitiligo&#44; pois o gen&#243;tipo GG DEFB1 &#40;&#8722;20G&#47;A&#41; e o alelo G contribuem para o desenvolvimento de vitiligo em popula&#231;&#245;es eg&#237;pcias&#46; A diminui&#231;&#227;o dos n&#237;veis circulantes de HBD&#8208;1 pode ter papel ativo na etiopatogenia do vitiligo&#44; que pode ser mediada por seus poss&#237;veis efeitos anti&#8208;inflamat&#243;rios&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Suporte financeiro</span><p id="par0225" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Contribui&#231;&#227;o dos autores</span><p id="par0230" class="elsevierStylePara elsevierViewall">Todos os autores devem ter feito contribui&#231;&#245;es substanciais para todos os itens a seguir&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Azza Gaber Antar Farag&#58; Revis&#227;o cr&#237;tica da literatura&#59; concep&#231;&#227;o e planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Mohamed Abd Al Moneam Shoaib&#58; Concep&#231;&#227;o e planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Azza Zagloul labeeb&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Asmaa Shaaban Sleem&#58; Interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Hagar Mahmoud AbdElkader Khallaf&#58; Obten&#231;&#227;o de dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Amany Salah Khalaf&#58; An&#225;lise e interpreta&#231;&#227;o dos dados&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Mustafa Elsayed Elshaib&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Nada Farag Elnaidany&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Hayam Mohamed Aboelnasr Hanout&#58; Planejamento do estudo&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflito de interesses</span><p id="par0280" 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">O vitiligo &#233; doen&#231;a adquirida caracterizada por despigmenta&#231;&#227;o da pele&#44; que tem fundo gen&#233;tico e autoimune&#46; A beta&#8208;defensina&#8208;1 humana &#40;HBD&#8208;1&#41; e seu polimorfismo g&#234;nico foram associados a alguns dist&#250;rbios autoimunes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Elucidar o poss&#237;vel papel da HBD&#8208;1 na patog&#234;nese do vitiligo n&#227;o segmentar &#40;VNS&#41; por meio da avalia&#231;&#227;o dos n&#237;veis s&#233;ricos da HBD&#8208;1 e seu polimorfismo de nucleot&#237;deo &#250;nico &#40;SNP&#41; em pacientes com VNS&#44; al&#233;m de correlacionar os resultados com a extens&#227;o do vitiligo nesses pacientes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Um estudo de caso&#8208;controle com inclus&#227;o de 50 pacientes com VNS e 50 controles&#46; O escore <span class="elsevierStyleItalic">Vitiligo Area Scoring Index</span> &#40;VASI&#41; foi utilizado para avaliar a gravidade da doen&#231;a e investiga&#231;&#245;es laboratoriais foram realizadas para avaliar os n&#237;veis s&#233;ricos de HBD&#8208;1 utilizando ELISA e o SNP da defensina&#8208;beta1 &#40;DEFB1&#41; por an&#225;lise de polimorfismo de fragmentos de restri&#231;&#227;o utilizando a rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#8208;RFLP&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de HBD&#8208;1 significantemente mais baixos foram observados nos casos de VNS do que nos controles &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Houve predomin&#226;ncia significante do gen&#243;tipo GG DEFB1 e do alelo G nos pacientes com VNS em rela&#231;&#227;o aos controles &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Os n&#237;veis s&#233;ricos dos gen&#243;tipos HBD&#8208;1 e DEFB1 n&#227;o foram associados ou correlacionados de maneira significante com nenhum dos par&#226;metros pessoais e cl&#237;nicos dos pacientes com vitiligo&#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">O pequeno tamanho da amostra&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O polimorfismo do gene DEFB1 &#40;gen&#243;tipo GG e alelo G&#41; pode modular o risco de vitiligo e contribuir para o desenvolvimento de vitiligo em popula&#231;&#245;es eg&#237;pcias&#46; A diminui&#231;&#227;o dos n&#237;veis circulantes de HBD&#8208;1 pode ter papel ativo na etiopatogenia do vitiligo&#44; que pode ser mediada por seus poss&#237;veis efeitos anti&#8208;inflamat&#243;rios&#46;</p></span>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8208;&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">118&#44;69</td><td class="td" title="\n
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                  \t\t\t\t">46&#44;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;00&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">N&#237;vel s&#233;rico de HBD&#8208;1 em rela&#231;&#227;o aos gen&#243;tipos de beta&#8208;defensina humana&#8208;1 em pacientes com vitiligo e grupo controle</p>"
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                          "autores" => array:6 [
                            0 => "Z&#46;A&#46; Abdel-Malek"
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                            5 => "I&#46; Hamzavi"
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                    0 => array:2 [
                      "doi" => "10.1111/pcmr.12878"
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                        "tituloSerie" => "Pigment Cell Melanoma Res&#46;"
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                        "volumen" => "33"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emerging role of immune cell network in autoimmune skin disorders&#58; an update on pemphigus&#44; vitiligo&#44; and psoriasis"
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                          "etal" => false
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                            4 => "A&#46; Sharma"
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                    0 => array:2 [
                      "doi" => "10.1016/j.cytogfr.2019.01.001"
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                        "tituloSerie" => "Cytokine Growth Factor Rev&#46;"
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                        "paginaInicial" => "35"
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                      "titulo" => "Antimicrobial peptides&#8208;promising alternatives to conventional antibiotics"
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                    0 => array:2 [
                      "doi" => "10.1159/000331009"
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                        "tituloSerie" => "J Mol Microbiol Biotechnol&#46;"
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                        "volumen" => "20"
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                            5 => "J&#46; Horba&#324;czuk"
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                    0 => array:2 [
                      "doi" => "10.1016/j.humimm.2013.05.008"
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                    0 => array:2 [
                      "doi" => "10.1159/000336619"
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                        "volumen" => "4"
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                        "paginaFinal" => "348"
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                      "titulo" => "Construction of recombinant E&#46; coli Nissle 1917 &#40;EcN&#41; strains for the expression and secretion of defensins"
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ISSN: 26662752
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