Increased serum levels of soluble fractalkine (CX₃CL1) correlate with disease activity in rheumatoid vasculitis

Abstract

OBJECTIVE: To determine levels of soluble fractalkine (sFkn) in rheumatoid arthritis (RA) patients with and without rheumatoid vasculitis (RV), and to assess the relationship of sFkn levels to disease activity. METHODS: Serum was obtained from 98 RA patients (54 without vasculitis, 36 with extraarticular manifestations but without histologically proven vasculitis, and 8 with histologically proven vasculitis) and from 38 healthy individuals. Levels of sFkn were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified by real-time polymerase chain reaction. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score and the Vasculitis Activity Index. RESULTS: Serum sFkn levels were significantly higher in patients with RA than in controls and were significantly higher in RA patients with RV than in those without vasculitic complications. Statistically significant correlations were observed between serum sFkn levels in RA patients and levels of C-reactive protein, rheumatoid factor, immune complex, and complement. In the RV group, sFkn levels also correlated with disease activity. Immunohistochemical analysis indicated that Fkn levels were associated mainly with endothelial cells in vasculitic arteries. In addition, expression of CX(3)CR1 messenger RNA was significantly greater in peripheral blood mononuclear cells from patients with active RV than in those from other RA patients or controls. Notably, serum sFkn levels were significantly diminished following successful treatment and clinical improvement. CONCLUSION: These findings suggest that Fkn and CX(3)CR1 play crucial roles in the pathogenesis of RV and that sFkn may serve as a serologic inflammatory marker of disease activity in RA patients with vasculitis.