Background TL1A (TNFSF15) is a newly identified TNF-like cytokine that associates with the death domain receptor DR3 (TNFRSF25), expressed on activated lymphocytes. TL1A-DR3 binding produces costimulatory signals resulting in lymphocyte proliferation, secretion of pro-inflammatory cytokines and induction of apoptotic signals . Recent studies have shown that both TL1A and DR3 are upregulated and possibly implicated in the pathogenesis of several chronic inflammatory conditions, including, inflammatory bowel disease, rheumatoid arthritis, and psoriasis [2, 3].
Objectives (a) To examine whether soluble TL1A is increased in Ankylosing Spondylitis (AS). (b) To search for possible correlations between TL1A serum concentration, and various clinical and laboratory parameters of AS. (c) To study the effect of anti-TNF treatment on soluble TL1A levels.
Methods Seventy-five consecutive patients with AS (61 men), aged 47.2±15.5 years (mean±SD) with disease duration of 20.3±13.9 years, were included in this cross-sectional study. Nineteen age and sex-matched healthy individuals served as controls. Forty four patients were anti-TNF treatment-naïve, whereas the remaining patients were on infliximab (n=21), adalimumab (n=3), or etanercept (n=7). The patients’ perceived disease activity and functional limitation were recorded by Bath AS Disease Index (BASDAI) and Bath AS Functional Index (BASFI) respectively. The objective functional status was evaluated by measurements of spinal mobility (AS-Metrology). Serum concentrations of TL1A were measured by ELISA. Mann-Whitney two-sample statistics was used for group comparisons and Spearman’s coefficients for testing correlation between variables.
Results Average serum concentration of TL1A were 3-fold higher in anti-TNF- naïve (601±1066 pg/ml) compared to anti-TNF-treated patients (196±302 pg/ml, p=0.018) and healthy controls (199±286 pg/ml, p=0.03). No significant association between individual TL1A serum levels and functional status (BASFI-score, AS metrology parameters), presence of extra-articular manifestations such as intestinal inflammation and uveitis, or C-reactive protein levels measured in the same individual was found. A positive correlation between individual serum levels of TL1A and BASDAI scores was noted (Spearman r=0.3, p=0.01).
Conclusions We report increased serum concentrations of TL1A in AS which correlate with clinical disease activity and can be controlled by anti-TNF treatment. Interactions between TL1A and its receptors may be important in the pathogenesis of the disease.
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Disclosure of Interest None Declared
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