Complement activion in patients with RA mediated in part by c-reactive protein.

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Arthritis Rheum 2001 May;44(5):997-1002

Complement activation in patients with rheumatoid arthritis mediated in part by

C-reactive protein.

Molenaar ET, Voskuyl AE, Familian A, van Mierlo GJ, Dijkmans BA, Hack CE.

Vrije Universiteit Medical Center, Amsterdam, The Netherlands.

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. 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.