Relevance of circulating Semaphorin 4A for rheumatoid arthritis progression and response to treatment

Abstract

Abstract The lack of validated tools to predict rheumatoid arthritis (RA) disease course warrants the development of new reliable biomarkers. Our aim was to evaluate the merit of circulating SEMA4A for the prediction of outcomes in patients with RA. In a first cohort of 101 consecutive RA patients followed up for 41±15 months, increased baseline SEMA4A levels were identified as an independent predictor of disease progression (hazard ratio, HR: 2.71, 95%CI 1.14–6.43), defined by the occurrence of patient-reported flares and initiation or change of targeted therapy. The highest predictive value of disease progression was obtained with the combination of increased circulating SEMA4A and/or Disease Activity Score (DAS) 28-CRP > 3.2 and/or synovial hyperemia on doppler ultrasound (HR: 10.42, 95%CI 1.41–76.94). In a second independent cohort of 40 consecutive RA patients who initiated new therapy because of insufficient disease control, baseline SEMA4A levels were significantly higher in patients who further experienced none or moderate response, and SEMA4A concentrations were markedly decreased in the group of patients with good clinical response as compared to non-responders. Circulating SEMA4A appears as an appealing biomarker in RA with ability to predict disease progression, and with association with response to therapy.