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

Objective. 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. W e therefore hypothesized that part of the complement activation in RA is du e to CRP. The aim of this study was to investigate CRP-mediated complement activation in RA, and to assess its correlation with disease activity. Methods. Complexes between CRP and the activated complement components CM ( C3d-CRP) and C4d (C4d-CRP), which reflect CRP-mediated complement activatio n, as well as the overall levels of activated C3 and C4 were measured in th e plasma of 107 patients with active RA and 177 patients with inactive RA. Inactive RA was defined according to the American College of Rheumatology c riteria for clinical remission. Disease activity was assessed by the modifi ed Disease Activity Score (DAS28). Results. Plasma levels of C3d-CRP and C4d-CRP were increased in the majorit y of the patients, and were significantly higher in patients with active di sease 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), wh ereas 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). Level s of activated C3 and C4 were also increased in the majority of the patient s, particularly in patients with active RA. Conclusion. Part of the activation of complement in RA is mediated by CRP a nd is correlated with disease activity. We suggest that this activation is involved in the pathogenesis of RA.