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Doctoral Thesis
Full name
Renata Casseb de Souza Carboni
Knowledge Area
Date of Defense
São Paulo, 2021
Shinjo, Samuel Katsuyuki (President)
Aikawa, Nádia Emi
Machado, Ketty Lysie Libardi Lira
Rocha Junior, Laurindo Ferreira da
Title in Portuguese
Aumento das concentrações séricas de YKL-40 e sua expressão nos tecidos musculares de pacientes com síndrome antissintetase
Keywords in Portuguese
Biópsia muscular
Miopatia inflamatória
Síndrome antissintetase
Abstract in Portuguese
Introdução. A proteína 1 similar à quitinase-3 (YKL-40) tem sido associada a diversos processos fisiológicos, como inflamação, angiogênese, proliferação celular, fibrose e remodelação tecidual. O aumento da concentração sérica de YKL-40 tem sido descrito em várias doenças autoimunes sistêmicas, exceto na síndrome antissintetase (SAS). Objetivos. Avaliar a concentração sérica de YKL-40 em pacientes com SAS, e correlacioná-la com parâmetros demográficos, laboratoriais e clínicos, status de doença e tratamento medicamentoso. Por fim, avaliar a expressão de YKL-40 nos tecidos musculares destes pacientes. Métodos. Trata-se de um estudo transversal, unicêntrico, de 2017 a 2019, que incluiu 64 pacientes adultos com SAS pareados por idade, sexo e etnia com 64 controles saudáveis. As concentrações séricas da YKL-40 foram avaliadas pelo método ELISA, enquanto a expressão da YKL-40 nos tecidos musculares foi analisada por técnica de imuno-histoquímica na biópsia de 5 pacientes. O status de doença foi avaliado pelo escore de Myositis Disease Activity Assessment Visual Analogue Scales. Resultados. A média de idade dos pacientes foi de 44,8±11,8 anos, com duração mediana da doença de 1,5 (0,0-4,0) anos. Os pacientes eram predominantemente do sexo feminino (82,8%) e brancos (73,4%), comparáveis ao grupo controle. A maioria dos pacientes apresentava doença estável. A mediana da concentração sérica de YKL-40 foi maior no grupo SAS do que no grupo controle: 538,4 (363,4-853,1) pg/mL versus 270,0 (201,8-451,9) pg/mL, respectivamente; P<0,001. No entanto, após análise multivariada, a YKL-40 não se correlacionou com nenhum parâmetro clínico, laboratorial, status de doença ou terapêutica (P>0.05), exceto com a concentração sérica de fator de necrose tumoral (TNF-) (correlação de Spearman: rho=0.382; P=0.007). A YKL-40 estava expressa em tecidos musculares com a presença de infiltrados de células inflamatórias. Conclusões. Pacientes com SAS apresentam alta concentração sérica de YKL-40, a qual se correlacionou positivamente com a de TNF-. No entanto, não houve correlação entre os níveis séricos da YKL-40 com os parâmetros demográficos, status de doença, autoanticorpos, comorbidades ou parâmetros terapêuticos. Além disso, a YKL-40 mostrou-se expressa em tecidos musculares com infiltrados de células
Title in English
Increased serum concentrations of YKL-40 and its expression in the muscle tissues of patients with antisynthetase syndrome
Keywords in English
Antisynthetase syndrome
Inflammatory myopathy
Muscle biopsy
Abstract in English
Introduction. Chitinase-3-like-1 protein (YKL-40) has been associated with many physiological processes, such as inflammation, angiogenesis, cell proliferation, tissue fibrosis, and remodeling. High serum levels of YKL-40 have been described in several systemic autoimmune diseases, but there is still no description of this glycoprotein in antisynthetase syndrome (ASS). Objectives. To evaluate YKL-40 serum levels, correlate them with laboratory and clinical parameters, disease status and treatment schemes, and analyze the YKL-40 expression in the muscle tissues of these patients. Methods. This cross-sectional single-center study, from 2017 to 2019, that included 64 adult patients with ASS, who were age-, gender- and ethnicity-matched to 64 controls. The serum levels of the YKL-40 analysis were performed by ELISA kit method, whereas the YKL-40 expression in muscle tissues was analyzed by an immunohistochemistry technique in the biopsy of 5 patients. The disease status was assessed by the International Myositis Assessment and Clinical Studies Group set scores. Results. The patients mean age was 44.8±11.8 years, and median disease duration of 1.5 (0.0-4.0) years. These patients were predominantly female (82.8%) and White (73.4%). Most patients had stable disease. The median YKL-40 serum level was significantly higher in the ASS patients when compared to the healthy individuals: 538.4 (363.4-853.1) pg/mL versus 270.0 (201.8-451.9) pg/mL, respectively; P<0.001. However, through multivariate, analysis YKL-40 serum levels did not correlate with any clinical, laboratory, disease status, or therapeutic parameters (P>0.050), except tumor necrosis factor alpha serum levels (TNF-) (Spearmans correlation, rho=0.382; P=0.007). YKL-40 was highly expressed by inflammatory cells found in muscle biopsy specimens. Conclusions. High YKL-40 serum levels were observed in patients with ASS and correlated positively with TNF- serum levels. However, YKL-40 serum levels did not correlate with any demographic parameters, disease status, autoantibodies, comorbidities, or therapeutic parameters. Moreover, YKL-40 was expressed in muscle tissues with inflammatory cells
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