Circulating levels of TL1A and its decoy receptor DcR3 in systemic sclerosis.

INTRODUCTION/OBJECTIVE: Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is a profibrotic and proinflammatory cytokine. Experimental evidence implicates TL1A-mediated interactions in interstitial lung disease (ILD); such interactions are disrupted by decoy receptor 3 (DcR3) binding to TL1A. We examined the potential clinical value of circulating TL1A and DcR3 levels in systemic sclerosis (SSc). METHODS: Consecutive unselected patients with SSc (n = 41) of varying disease duration, severity, and treatment modalities; individuals with primary Raynaud's phenomenon (pRP) (n = 52); and apparently healthy individuals (n = 49) were studied. Serum TL1A and DcR3 levels were measured by ELISA. RESULTS: TL1A levels were increased in SSc patients compared to healthy individuals whereas DcR3 levels were increased in SSc compared to both pRP and healthy individuals (all p < 0.001). Clinical features, pulmonary function tests, and treatment modalities were analyzed at baseline and annually for two consecutive years. Using receiver operating characteristic (ROC) analysis and the MINIMISE endpoint for mortality and morbidity we found that baseline serum levels of DcR3, but not TL1A, were predictive of SSc progression over 2 years (AUC = 0.684, p = 0.04). While no associations between TL1A levels and disease characteristics were noted, patients with DcR3 levels above the ROC-defined cut-off had significantly higher erythrocyte sedimentation rate, higher prevalence of ILD confirmed by high resolution chest computed tomography, and lower diffusion capacity for carbon monoxide. CONCLUSIONS: Increased circulating DcR3 levels are associated with SSc-ILD in unselected patients and may serve as a biomarker of disease progression. Further studies are needed to explore the clinical value in selected SSc patient subgroups. Keypoints • TL1A and DcR3 are elevated in the serum of patients with systemic sclerosis. • DcR3 levels are associated with SSc-ILD and higher systemic inflammation. • Circulating DcR3 levels may serve as a prognostic biomarker in SSc.