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PLoS One ; 13(5): e0197001, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29787569

RESUMO

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit. CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Processamento de Imagem Assistida por Computador/métodos , Interleucina-6/análise , Membrana Sinovial/patologia , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/metabolismo , Estudos de Casos e Controles , Quimiocina CCL2/metabolismo , Feminino , Humanos , Técnicas In Vitro , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Técnicas de Cultura de Tecidos , Ultrassonografia Doppler em Cores/métodos
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