Níveis séricos de citocinas na arterite de Takayasu, há algum padrão de resposta predominante?
Arquivos
Data
2017-12-13
Autores
Fernandez, Bruna Savioli Lopez 
Orientadores
Souza, Alexandre Wagner Silva de
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução – A arterite de Takayasu (AT) é uma vasculite granulomatosa crônica de grandes vasos que afeta a aorta e seus principais ramos. Níveis séricos de citocinas podem ser utilizados como biomarcadores para auxiliar na detecção de atividade de doença subclínica na AT. Objetivos – Avaliar níveis séricos de citocinas pró-inflamatórias (TNFα, IL-1β e IL-6), de citocinas anti-inflamatórias (IL-2 e IL-10) e de citocinas envolvidas na resposta Th1 (IFNγ e IL-12p70), Th2 (IL-4, IL-5 e IL-13), Th9 (IL-9), Th17 (IL-17A, IL-17E ou IL-25, IL-17F, IL-21 e IL-23) e Th22 (IL-22) em pacientes com AT em remissão e em controles saudáveis. Avaliar associações entre níveis séricos de citocinas de pacientes com AT em remissão e variáveis clínicas. Pacientes e métodos – Realizamos estudo de corte transversal incluindo 34 pacientes com AT com doença inativa e sem mudança de terapia há 6 meses e 20 controles. Amostras de soro foram armazenadas a -80°C para a dosagem de citocinas pela técnica de multiplex. As seguintes citocinas foram avaliadas: TNFα, IL-1β, IL-6, IL-2, IL-10, IFNγ, IL-12p70, IL-4, IL-5, IL-13, IL-9, IL-17A, IL17E, IL17F, IL-21, IL-23 e IL-22. Resultados – Pacientes com AT em remissão apresentaram níveis séricos de citocinas semelhantes aos dos controles. Os níveis séricos de TNFα, IL-17F, IL-21 e IL-23 foram significativamente mais elevados em pacientes com tipo arteriográfico V em comparação àqueles com outros tipos arteriográficos. Níveis séricos de IL-17E, IL-17F, IL-22 e IL-23 foram significativamente mais elevados em pacientes com histórico de eventos isquêmicos comparados aos sem eventos prévios. Foram observadas associações independentes entre tipo arteriográfico V e maiores níveis séricos de IL-4, IL-6, IL-17A, IL-17E, IL-17F, IL-21 e IL-23. Eventos isquêmicos prévios se associaram de forma independente aos níveis séricos de IL-4, IL-17F e IL-23. Conclusões – Os achados do estudo salientam a importância da resposta Th17 na fisiopatologia da AT, mesmo em pacientes em remissão clínica, e podem fornecer dados importantes para se estudar novos alvos terapêuticos.
Introduction – Takayasu arteritis (TA) is a chronic granulomatous vasculitis of large vessels that affects the aorta and its main branches. Serum cytokines levels may be surrogate markers of subclinical disease activity TA. Objective – To evaluate serum levels of proinflammatory cytokines (TNFα, IL-1β and IL-6), anti-inflamatory cytokines (IL-2 and IL-10) and serum levels of cytokines involved in Th1 (IFNγ and IL-12p70), Th2 (IL-4, IL-5 and IL-13), Th9 (IL-9), Th17 (IL-17A, IL- 17E, IL-17F, IL-21 and IL-23) and in Th22 (IL-22) responses in TA patients during remission and compare with healthy controls. To evaluate associations between serum levels of cytokines and clinical disease features and therapy for TA. Patients and methods – A cross-sectional study was performed including 34 TA patients in remission and 20 controls. Serum samples were stored at -80°C before measuring serum cytokine levels by multiplexing technique. The following cytokines were evaluated: IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17A, IL- 17E, IL-17F, IL-21, IL-22 and IL-23. Results – TA patients in remission showed similar cytokines levels to that of controls. Serum levels of TNFα, IL-17F, IL-21 and IL-23 were significantly higher in TA patients presenting angiographic type V compared with patients presenting other angiographic types. In addition, TA patients with previous ischemic events presented higher IL-17E, IL-17F, IL-22 and IL-23 than TA patients without this complication. Independent associations were observed between angiographic type V and serum levels of IL-4, IL- 6, IL-17A, IL-17E, IL-17F, IL-21 and IL-23. Previous ischemic events were independently associated with IL-4, IL-17F and IL-23 serum levels. Conclusions – These findings emphasize the role of the Th17 response in the pathophysiology of TA, even in patients considered in clinical remission, and may provide important clues for the assessment of novel therapeutic targets in TA.
Introduction – Takayasu arteritis (TA) is a chronic granulomatous vasculitis of large vessels that affects the aorta and its main branches. Serum cytokines levels may be surrogate markers of subclinical disease activity TA. Objective – To evaluate serum levels of proinflammatory cytokines (TNFα, IL-1β and IL-6), anti-inflamatory cytokines (IL-2 and IL-10) and serum levels of cytokines involved in Th1 (IFNγ and IL-12p70), Th2 (IL-4, IL-5 and IL-13), Th9 (IL-9), Th17 (IL-17A, IL- 17E, IL-17F, IL-21 and IL-23) and in Th22 (IL-22) responses in TA patients during remission and compare with healthy controls. To evaluate associations between serum levels of cytokines and clinical disease features and therapy for TA. Patients and methods – A cross-sectional study was performed including 34 TA patients in remission and 20 controls. Serum samples were stored at -80°C before measuring serum cytokine levels by multiplexing technique. The following cytokines were evaluated: IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17A, IL- 17E, IL-17F, IL-21, IL-22 and IL-23. Results – TA patients in remission showed similar cytokines levels to that of controls. Serum levels of TNFα, IL-17F, IL-21 and IL-23 were significantly higher in TA patients presenting angiographic type V compared with patients presenting other angiographic types. In addition, TA patients with previous ischemic events presented higher IL-17E, IL-17F, IL-22 and IL-23 than TA patients without this complication. Independent associations were observed between angiographic type V and serum levels of IL-4, IL- 6, IL-17A, IL-17E, IL-17F, IL-21 and IL-23. Previous ischemic events were independently associated with IL-4, IL-17F and IL-23 serum levels. Conclusions – These findings emphasize the role of the Th17 response in the pathophysiology of TA, even in patients considered in clinical remission, and may provide important clues for the assessment of novel therapeutic targets in TA.
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Citação
FERNANDEZ, Bruna Savioli Lopez. Níveis séricos de citocinas na arterite de Takayasu, há algum padrão de resposta predominante?. São Paulo, 2017. [91] p. Dissertação (Mestrado em Ciências da saúde aplicadas à reumatologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2017.