• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2024.tde-22042024-113654
Document
Author
Full name
Alessandra Anzai
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2024
Supervisor
Committee
Aoki, Valeria (President)
Ramos, Paulo Müller
Sotto, Mirian Nacagami
Valente, Neusa Yuriko Sakai
Title in Portuguese
Análise da expressão de HLA-G, TLR 2, 3, 4 e 5 e Cav-1 no folículo piloso do couro cabeludo de pacientes com líquen plano pilar
Keywords in Portuguese
Alopecia
Antígenos HLA-G
Caveolina-1
Líquen plano
Receptores toll-like
Abstract in Portuguese
Introdução: O líquen plano pilar (LPP) é uma alopecia cicatricial primária que causa grande impacto na qualidade de vida pela perda irreversível de cabelos e presença de prurido, ardor e dor. A histopatologia é caracterizada por inflamação liquenoide que agride o folículo piloso (FP), especificamente no istmo, onde residem as células-tronco foliculares. A etiopatogenia é desconhecida e consequentemente os tratamentos são pouco eficazes. Objetivos: Avaliar a expressão de toll-like receptors 2, 3, 4 e 5 (TLR2, TLR3, TLR4, TLR5), do Antígeno Leucocitário Humano G (HLA-G) e de Caveolina-1 (Cav-1), em espécimes de couro cabeludo de pacientes com LPP forma clássica, tanto nas áreas clinicamente afetadas (LPP-A) quanto nas áreas clinicamente não afetadas (LPP-NA), em comparação com controles saudáveis (CS) e correlacionar a expressão dos marcadores com o índice de atividade de LPP (LPPAI) e com a intensidade do infiltrado inflamatório. Métodos: As 31 amostras LPP-A (n=10), LPP-NA (n=10) e CS (n=11) foram submetidas a estudo anatomopatológico, imuno-histoquímico e/ou imunofluorescência. Os testes estatísticos de correlação de Spearman. análise de variância (ANOVA) de duas vias e teste de Tukey foram analisados pelo software GraphPadPrism 10.0. Resultados: O TLR2 e o TLR3 expressam padrão citoplasmático em todo o FP, exceto na bainha radicular interna (BRI). O TLR3 no istmo tem expressão mais intensa nos CS, intermediária em LPP-NA e menos intensa em LPP-A. A expressão de TLR3 em LPP-A tem correlação forte negativa com LPPAI. A expressão de TLR4 e TLR5 tem padrão citoplasmático, presente na camada basal no infundíbulo, em todas as camadas da bainha radicular externa (BRE) na região de istmo e suprabulbar, presente discretamente na BRI e ausente no bulbo. O HLA-G expressa padrão citoplasmático na camada granulosa no infundíbulo, padrão perinuclear na BRE no istmo, suprabulbar e bulbo, e é ausente na BRI. A Cav-1 expressa padrão membranoso na camada basal no infundíbulo, camada basal da BRE na região do istmo, é ausente na BRI e discretamente positiva na BRE na região suprabulbar e bulbo. Na avaliação anatomopatológica, amostras de LPP-NA apresentam infiltrado inflamatório ao redor do istmo de intensidade equivalente ou menor que LPP-A. Infiltrado inflamatório ao redor do istmo, degeneração vacuolar do epitélio folicular, hiperqueratose periosteal, infiltrado perifolicular rechaçado por fibrose e fibrose eosinofílica estão presentes em amostras de CS. Conclusão: A expressão de HLA-G, TLR 2, 3, 4 e 5 e Cav-1 varia em intensidade e padrão de acordo com a região do FP. Dentre eles destaca-se o TLR3 que é expresso no istmo dos controles saudáveis, está diminuído na área não afetada e tem ainda menor expressão na área afetada. Pesquisas futuras poderão confirmar seu papel na fisiopatologia do LPP e sua relevância como marcador diagnóstico e prognóstico desta enfermidade
Title in English
Analysis of the expression of HLA-G, TLR 2, 3, 4 and 5 and Cav-1 within the scalp hair follicle of patients with lichen planopilaris
Keywords in English
Alopecia
Caveolin-1
HLA-G antigens
Lichen planopilaris
Toll-like receptor
Abstract in English
Introduction: Lichen planopilaris (LPP) is a primary cicatricial alopecia that causes a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. Histopathology findings show a lichenoid infiltration to the hair follicle (HF), specifically around the isthmus, where the follicular stem cells reside. The etiopathogenesis is unknown and consequently the treatments are poorly effective. Objectives: To evaluate the expression of toll-like receptors 2, 3, 4 and 5 (TLR2, TLR3, TLR4, TLR5), Human Leukocyte Antigen G (HLA-G) and Caveolin-1 (Cav-1) in scalp biopsies of patients with classic form of LPP, both in clinically affected areas (LPP-A) and in clinically nonaffected areas (LPP-NA) in comparison with healthy controls (HC) and correlate the expression of these markers with the LPP activity index (LPPAI) and the intensity of the inflammatory infiltrate. Methods: The analysis of the 31 samples of LPP-A (n=10), LPP-NA (n=10) and HC (n=11) included histopathology, immunohistochemistry and/or immunofluorescence study. Spearman's statistical correlation test, two-way analysis of variance (ANOVA) and Tukey test were analyzed using GraphPadPrism 10.0 software. Results: TLR2 and TLR3 express a cytoplasmic pattern throughout the HF, except in the inner root sheath (IRS). TLR3 in the isthmus is more intensely expressed in HC, moderately expressed in LPP-NA and less intensely expressed in LPP-A. TLR3 expression in LPP-A has a strong negative correlation with LPPAI. The expression of TLR4 and TLR5 has a cytoplasmic pattern, present in the basal layer in the infundibulum, in all layers of the outer root sheath (ORS) in the isthmus and suprabulbar region, weakly present in the IRS and absent in the bulb. HLA-G expresses a cytoplasmic pattern in the granular layer in the infundibulum, a perinuclear pattern in the ORS in the isthmus, suprabulbar and bulb, and is absent in the IRS. Cav-1 expresses a membranous pattern in the basal layer in the infundibulum, basal layer of the ORS in the isthmus region, is absent in the IRS and weakly positive in the ORS in the suprabulbar region and bulb. In histopathology evaluation, LPP-NA samples present an inflammatory infiltrate around the isthmus of equivalent or lower intensity than LPP-A. Perifollicular lymphocytic infiltrate around the isthmus, vacuolar degeneration of the follicular epithelium, periosteal hyperkeratosis and eosinophilic fibrosis are present in HC samples. Conclusion: The expression of HLA-G, TLR 2, 3, 4 and 5 and Cav-1 varies in intensity and pattern according to the HF region. Among them, TLR3 stands out for being expressed in the isthmus of HC, and whose intensity is reduced in LPP-NA and is even less expressed in LPP-A. Future research may confirm its role in the pathophysiology of LPP and its relevance as a diagnostic and prognostic marker for this disease
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2024-04-29
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.