Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis

• We have followed patients with RA for 3.5 yrs for new atheromatic plaque formation.
• All patients had baseline serum concentration measurement for TL1A and DcR3.
• High TL1A concentration correlated with progression in plaque height at 3.5 years.
• Low TL1A/undetectable DcR3 serological profile predicted lack of atherogenesis.
• The TL1A/DR3/DcR3 system may contribute to accelerated atherogenesis in RA.

Interactions between TNF-like Cytokine 1A (TL1A) and its receptors, death receptor-3 (DR3) and decoy receptor-3 (DcR3) may be important in atherogenesis. We hypothesized that dysregulation of this system predicts formation of new atheromatic plaques in rheumatoid arthritis (RA). Forty-five patients were prospectively followed up for 40.5 ± 3.6 months. Serum concentrations of TL1A and DcR3 were measured at baseline and carotid and femoral arteries examined by ultrasound at baseline and at the end of follow-up. Individual serum levels of TL1A correlated with the progression of carotid atheromatic plaque height (Spearman rho = 0.550, p = 0.003). Patients with low TL1A and undetectable DcR3 serum levels at baseline showed significantly fewer newly formed carotid plaques during the next 3.5 years than the remaining patients (P = 0.016). Univariate analysis showed that a “low TL1A/DcR3” immunophenotype predicted a preserved atherosclerosis profile in carotid (P = 0.026), or carotid and/or femoral arteries (P = 0.022). Dysregulated TL1A-induced signaling may be associated with risk for accelerated atherosclerosis in RA.