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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-09022021-100253
Document
Author
Full name
Gabriela Franco Marques
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Criado, Paulo Ricardo (President)
Belda Junior, Walter
Chiacchio, Nilton Di
Romiti, Ricardo
Title in Portuguese
Avaliação  das populações de macrófagos de fenótipo M1/M2 e marcadores de ativação do inflamassoma em pacientes com poliarterite nodosa cutânea
Keywords in Portuguese
Arterite
Ativação de macrófagos
Imunidade inata
Inflamassomos
Macrófagos
Poliarterite nodosa
Vasculite
Abstract in Portuguese
INTRODUÇÃO: A poliarterite nodosa cutânea (PANC) ou arterite cutânea é uma rara forma de vasculite que compromete artérias de pequeno e médio calibre da junção dermo-hipodérmica e tecido celular subcutâneo. Atualmente, acredita-se que a doença seja mediada por imunocomplexos, mas pouco se sabe a respeito da sua real etiologia. OBJETIVO: Estudar as populações de macrófagos de fenótipo M1/M2 e marcadores de ativação do inflamassoma em pacientes com PANC. MÉTODOS: Foram selecionados 14 pacientes com diagnóstico clínico e histopatológico de PANC, cujos dados epidemiológicos, clínicos e de exames laboratoriais foram coletados a partir dos prontuários médicos. Em seguida, foram feitos cortes histológicos a partir dos blocos de parafina da biópsia de pele dos pacientes com PANC e de mais 9 controles sem doença para a realização das reações de imuno-histoquímica. Os macrófagos M1 foram demonstrados pela expressão do STAT1, enquanto os macrófagos M2 foram evidenciados pelos marcadores CD163, CD206 e CMAF. A ativação do inflamassoma foi demostrada pelos anticorpos NALP1, NALP3, IL1-beta e caspase 1. RESULTADOS: Houve predomínio da doença em pacientes do sexo feminino com idade média de 39 anos. As principais lesões dermatológicas registradas foram úlceras, nódulos subcutâneos, livedo racemosa, lesões do tipo atrofia branca e púrpuras, e em todos os casos os membros inferiores estavam acometidos. A imunofluorescência direta foi positiva em 88,9% dos casos. A análise imuno-histoquímica das biópsias de pacientes do grupo PANC evidenciou ausência de macrófagos M1 e aumento no percentual de macrófagos M2 em relação ao grupo controle. A análise dos marcadores de ativação do inflamassoma foi negativa. CONCLUSÃO: A presença de macrófagos M2 sugere uma provável influência da imunidade inata na fisiopatologia da PANC e representa um novo campo de pesquisa para elucidar diversas questões que permanecem pendentes sobre a etiologia da doença, podendo ainda gerar potenciais alvos terapêuticos no futuro
Title in English
Study of macrophage polarization and inflammasome activation in patients with cutaneous polyarteritis nodosa
Keywords in English
Arteritis
Immunity innate
Inflammasomes
Macrophages, Macrophage activation
Polyarteritis nodosa
Vasculitis
Abstract in English
INTRODUCTION: Cutaneous polyarteritis nodosa (CPAN) or cutaneous arteritis is a rare form of cutaneous vasculitis that affects small and medium sized arteries of the dermo-hypodermic junction and subcutaneous tissue. Despite the good prognosis, there are cases of difficult management with major complications. Currently, it is believed that the disease is mediated by immune complexes, but little is known about its real etiology. OBJECTIVE: To study the populations of macrophages of phenotype M1 / M2 and markers of inflammasome activation in CPAN patients. METHODS: 14 patients with clinical and histopathological diagnosis of CPAN were selected, whose epidemiological, clinical and laboratory exams data were collected from medical records. Then, histological cuts were made from the paraffin blocks of patients' skin biopsy and also from 9 controls without known disease to perform immunohistochemical reactions. The M1 macrophages were demonstrated by STAT1 expression, while the M2 macrophages were shown by the CD163, CD206 and CMAF markers. The activation of the inflammasome was demonstrated by the antibodies NALP1, NALP3, IL1beta and caspase 1. RESULTS: There was a predominance of the disease in female patients with an average age of 39 years. The main dermatological lesions recorded were ulcers, subcutaneous nodules, livedo racemosa, white atrophy scars and purple lesions, and in all cases the lower limbs were affected. Direct immunofluorescence was positive in 88.9% of cases. The immunohistochemical analysis of the CPAN patients' biopsies showed an absence of M1 macrophages and an increased percentage of M2 macrophages compares to the control group. The analysis of inflammasome activation markers was negative. CONCLUSION: The presence of M2 macrophages suggests a probable influence of innate immunity on the pathophysiology of PANC and represents a new field of research to elucidate several questions that remain pending on the etiology of the disease, which may also generate potential therapeutic targets in the future
 
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Publishing Date
2021-02-11
 
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