Serum levels of tumor necrosis factor-like cytokine 1A and its receptors, death receptor 3 and decoy receptor 3, in patients with spondyloarthropathies: preliminary results from a cross-sectional study.

Abstract

Introduction: Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) is a member of the TNF superfamily of cytokines, involved in regulation of the immune and inflammatory response. Recently, therapies aimed at blockade of the TL1A pathway have shown benefit in the treatment of inflammatory bowel diseases (IBDs). However, very little is known regarding activation of the TL1A axis in spondyloarthropathies (SpA), which are clinically and pathogenetically linked to IBDs. Our study investigated soluble forms of TL1A and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3), in the serum of patients with SpA, and evaluated potential associations between concentrations of the investigated molecules and clinical features of SpA.

Material and methods: Tumor necrosis factor-like cytokine 1A, DR3, and DcR3 concentrations were measured (using enzyme linked immunosorbent assay - ELISA) in the serum of 82 patients with SpA and 36 healthy controls.

Results: We found no significant difference in serum concentrations of TL1A or DR3 between the study and the control groups. However, we observed a significantly higher concentration of DcR3 (median [min.-max.]: 292.31 [93.241-13,862.10] pg/ml) in patients with SpA than in the controls (median [min.-max.]: 126.73 [10.68-1,482.74] pg/ml; p = 0.003). The DR/DcR ratio was significantly lower in patients with SpA (median [min.-max.]: 4.05 [0.14-235.39]) than in the controls (17.22 [0.00-750.66]; p = 0.002). Moreover, there were weak but significant correlations between serum concentrations of DcR and TL1A (Spearman's rho: 0.28, p < 0.05) and between DcR3 and C-reactive protein as well as erythrocyte sedimentation rate values (Spearman's rho: 0.25 and 0.24 respectively, p < 0.05 for both) in patients with SpA.

Conclusions: The results of our study indicate that the TL1A/DR3/DcR3 axis is activated in patients with SpA and may represent a new target for therapies in this group of diseases. Further studies are needed to confirm our data.