Complement activation in patients with rheumatoid arthritis mediated in part by C-reactive protein

Abstract

Complement activation in patients with rheumatoid arthritis (RA) is considered to be triggered by immune complexes. Recently, it was shown that C-reactive protein (CRP) can activate the complement system in vivo. We therefore hypothesized that part of the complement activation in RA is due to CRP. The aim of this study was to investigate CRP-mediated complement activation in RA, and to assess its correlation with disease activity. Complexes between CRP and the activated complement components C3d (C3d-CRP) and C4d (C4d-CRP), which reflect CRP-mediated complement activation, as well as the overall levels of activated C3 and C4 were measured in the plasma of 107 patients with active RA and 177 patients with inactive RA. Inactive RA was defined according to the American College of Rheumatology criteria for clinical remission. Disease activity was assessed by the modified Disease Activity Score (DAS28). Plasma levels of C3d-CRP and C4d-CRP were increased in the majority of the patients, and were significantly higher in patients with active disease versus those with inactive RA (P < 0.001). In patients with active RA, the plasma concentrations of C3d-CRP and C4d-CRP correlated significantly with the DAS28 (Spearman's rho 0.61 and 0.55, respectively; P < 0.001), whereas these correlations were less pronounced in patients with inactive RA (Spearman's rho 0.28 [P < 0.001] and 0.25 [P = 0.001], respectively). Levels of activated C3 and C4 were also increased in the majority of the patients, particularly in patients with active RA. Part of the activation of complement in RA is mediated by CRP and is correlated with disease activity. We suggest that this activation is involved in the pathogenesis of RA.