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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-10032020-141613
Document
Author
Full name
Marilda Guimarães Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Shinjo, Samuel Katsuyuki (President)
Teodoro, Walcy Paganelli Rosolia
Reis Neto, Edgard Torres dos
Souza, Fernando Henrique Carlos de
Title in Portuguese
Interleucina-17A como biomarcador da atividade da dermatomiosite e polimiosite
Keywords in Portuguese
Biomarcadores
Citocinas
Dermatomiosite
Interleucinas
Miosite
Polimiosite
Abstract in Portuguese
Introdução: Dermatomiosite (DM) e polimiosite (PM) são miopatias autoimunes sistêmicas que apresentam infiltrado de células inflamatórias nos tecidos musculares. Algumas citocinas pró-inflamatorias têm sido destacadas por estarem envolvidas na fisiopatogênese dessas doenças, a exemplo da interleucina (IL)-17A. Objetivos: Avaliar a concentração sérica de IL-17A em pacientes com DM e PM, e correlacioná-la com os dados demográficos, clínicos, laboratoriais, terapêuticos e status dessas doenças. Métodos: Estudo transversal que incluiu 80 pacientes adultos com DM e 32 com PM, no período de 2012 a 2016. Os pacientes foram pareados por sexo, etnia e idade com 104 indivíduos saudáveis. A análise de IL-17A sérica, assim como das demais citocinas (IL-6, TNF-Alfa e INF-Gama), foi realizada por imunoensaio multiplex. Os parâmetros do status da doença foram baseados nos escores estabelecidos por International Myositis Assessment & Clinical Studies Group (IMACS). Resultados: A média de idade dos pacientes com DM e PM foi de 46,0 ± 13,9 e 47,7 ± 14,3 anos, respectivamente, com predomínio de mulheres e cor branca em ambos os grupos. De modo geral, as características clínicas, laboratoriais, terapêuticas e status atual da doença foram semelhantes entre os pacientes com DM e PM. O nível mediano de IL-17A sérica foi maior nos pacientes com PM e DM em relação ao grupo controle [0,73 (0,53-1,14) vs. 0,49 (0,28-0,83) vs. 0,35 (0,09-0,61) pg/mL, respectivamente; P < 0,050] e maior em PM quando comparado a DM (P < 0,001). Em DM, os níveis de IL-17A sérica foram associados a lesões cutâneas cumulativas, parâmetros de IMACS e níveis de IL-6 e IFN-Gama séricos. Em PM o nível de IL-17A sérica correlacionou com a idade atual dos pacientes, parâmetros de IMACS e níveis de IFN-Gama e TNF-Alfa séricos. O nível de IL-17A sérica não correlacionou com o tratamento medicamentoso. Conclusões: A concentração sérica de IL-17A não está somente aumentada em pacientes com DM e PM, mas também associada a atividade dessas doenças. Os dados sugerem fortemente a IL-17A como possível biomarcador de atividade destas miopatias autoimunes sistêmicas
Title in English
Interleukin-17A as biomarker of disease activity of dermatomyositis and polymyositis
Keywords in English
Biomarkers
Cytokines
Dermatomyositis
Interleukins
Myositis
Polymyositis
Abstract in English
Introduction: Dermatomyositis (DM) and polymyositis (PM) are systemic autoimmune myopathies that show inflammatory cell infiltration in muscle tissues. Some pro-inflammatory cytokines have been highlighted for being involved in the pathophysiology of these diseases, such as interleukin (IL)-17A. Objectives: To assess serum levels of IL-17A in patients with DM and patients with PM and to correlate IL-17A with demographic, clinical, laboratory and therapeutic data, and disease status. Methods: This was a cross-sectional, single-center study that included patients with DM and patients with PM who were age-, gender- and ethnicity-matched to healthy individuals. Serum IL-17A analysis, as well as analysis for other cytokines (IL-6, TNF-Alpha and IFN-Gama), was performed by multiplex immunoassay. The disease status parameters were based on the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. Results: Mean age of patients with DM and patients with PM was 46.0 ± 13.9 and 47.7 ± 14.3 years, respectively, with a predominance of female and white ethnicity in both groups. Overall, clinical, laboratory, therapeutic, and current disease status were similar among patients with DM and patients with PM. Median serum levels of IL-17A was higher in patients with PM and patients with DM than the control group [0.73 (0.53-1.14) vs. 0.49 (0.28-0.83) vs. 0.35 (0.09-0.61) pg/mL; P < 0.050] and higher in PM when compared to DM (P < 0.001). In patients with DM, serum levels of IL-17A were associated with cumulative cutaneous lesions, IMACS parameters, and serum IL-6 and IFN-Gama levels. In patients with PM, serum IL-17A levels correlated with patients' current age, IMACS parameters and serum TNF-Alpha and IFN-Gama levels. Serum IL-17A level did not correlate with drug treatment. Conclusions: Serum levels of IL-17A are not only increased in patients with DM and patients with PM, but also associated with disease activity in patients with DM and patients with PM. The data strongly suggest IL17A as a possible biomarker of disease activity for these systemic autoimmune myopathies
 
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Publishing Date
2020-03-10
 
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