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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2021.tde-16082021-085915
Document
Author
Full name
Gustavo Luiz Behrens Pinto
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Shinjo, Samuel Katsuyuki (President)
Bezerra, Mailze Campos
Bonfiglioli, Karina Rossi
Pasoto, Sandra Gofinet
Title in Portuguese
Relevância da interleucina-17A sérica em síndrome antissintetase: estudo transversal e prospectivo
Keywords in Portuguese
Citocinas
Interleucina-17
Miopatias inflamatórias
Miosite
Síndrome antissintetase.
Abstract in Portuguese
Introdução: Síndrome antissintetase (SAS) é uma miopatia autoimune sistêmica com envolvimento muscular, pulmonar e articular, em associação a febre, "mãos de mecânico" e fenômeno de Raynaud. A citocina pró-inflamatória interleucina (IL)-17A sérica foi correlacionada a atividade de doença em diversas doenças autoimunes, incluindo outras miopatias autoimunes sistêmicas. Porém, o papel de IL-17A em síndrome antissintetase ainda não foi estabelecido. Objetivo: Avaliar a concentração sérica de IL-17A em pacientes com SAS em comparação com indivíduos saudáveis e correlacioná-la a dados demográficos, clínicos e laboratoriais. Secundariamente, analisar prospectivamente a concentração sérica de IL-17A em pacientes com SAS refratária submetidos a tratamento com rituximabe. Materiais e métodos: Trata-se de um estudo realizado no período de 2017 a 2019, constituído de duas fases: a) a IL-17A foi avaliada transversalmente em 64 pacientes com SAS, os quais foram pareados por idade, gênero e etnia com 64 controles saudáveis. Nesta fase foi analisada também a correlação da concentração sérica de IL-17A com dados demográficos, clínicos e laboratoriais; b) a IL-17A foi avaliada prospectivamente em pacientes com SAS refratária e que receberam rituximabe por um período de 12 meses. O status da doença foi mensurado pelo escore International Myositis Assessment & Clinical Studies Group. A IL-17A foi avaliada pelo método de enzyme linked immunosorbent assay. Resultados: A média de idade dos pacientes foi de 44,8±11,8 anos, com uma predominância do sexo feminino e etnia branca. A IL-17A estava aumentada em pacientes com SAS, quando comparada a do grupo controle: 9,7 (9,1-10,4) vs. 7,7 (5,79,0) pg/mL, respectivamente (P<0,001). Entretanto, as variáveis demográficas, clínicas e laboratoriais, incluindo os parâmetros de atividade de doença, não apresentaram correlação com a concentração sérica de IL-17A em pacientes com SAS. Prospectivamente, 16 pacientes receberam rituximabe e apresentaram uma queda de IL-17A ao longo de 12 meses de tratamento: 9,7 (9,1-10,6) vs. 9,0 (8,2-9,7) pg/mL (P=0,005). Conclusões: Pacientes com SAS apresentam aumento na concentração sérica de IL-17A, quando comparados com a de controles saudáveis. Além disto, os pacientes com SAS refratária tratados com rituximabe apresentam uma redução da concentração sérica de IL-17A no primeiro ano de tratamento.
Title in English
Relevance of serum interleukin-17A in antisynthetase syndrome: a crosssectional and prospective study
Keywords in English
Antisynthetase syndrome.
Cytokines
Inflammatory myopathies
Interleukin-17
Myositis
Abstract in English
Background: Antisynthetase syndrome (ASS) is a systemic autoimmune myopathy with muscular, pulmonary and joint involvement, in association with fever, mechanic's hands and Raynaud phenomenon. The serum proinflammatory cytokine interleukin (IL)-17A has been correlated with disease activity in several autoimmune diseases, including other systemic autoimmune myopathies. However, the role of IL-17A in ASS has not yet been established. Objectives: To assess the serum level of the IL-17A in patients with ASS compared to healthy individuals and to correlate it with demographic, clinical and laboratory data. Secondly, to analyze prospectively this IL in patients with refractory ASS undergoing treatment with rituximab. Methods: This is a study carried out from 2017 to 2019, consisting of two phases: a) IL-17A was assessed transversally in 64 patients with ASS, who were matched for age, gender and ethnicity with 64 healthy controls. In this phase, the correlation of the serum concentration of IL-17A with demographic, clinical and laboratory data were also analyzed; b) IL-17A was prospectively assessed in patients with refractory ASS who received rituximab for a period of 12 months. The disease status was measured using the International Myositis Assessment & Clinical Studies Group scores. IL-17A was evaluated using the enzyme linked immunosorbent assay method. Results: The mean age of the patients was 44.8±11.8 years, with a predominance of females and white ethnicity. IL-17A was increased in patients with ASS, when compared to the control group: 9.7 (9.1-10.4) vs. 7.7 (5.7-9.0) pg/mL, respectively (P<0.001). However, demographic, clinical and laboratory variables, including disease activity parameters, did not correlate with the serum concentration of IL-17A in patients with ASS. Prospectively, 16 patients received rituximab and experienced a drop in IL-17A over 12 months of treatment: 9.7 (9.1-10.6) vs. 9.0 (8.29.7) pg/mL (P=0.005). Conclusions: Patients with ASS show an increase in the serum concentration of IL-17A, when compared to that of healthy controls. In addition, patients with refractory ASS treated with rituximab experience a reduction in serum IL-17A concentration in the first year of treatment.
 
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Publishing Date
2021-08-16
 
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