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.
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.
Authors: Nicholas R Jones; Melissa A Pegues; Mark A McCrory; Steven W Kerr; Huiping Jiang; Rosemarie Sellati; Valentina Berger; Jorge Villalona; Rajvee Parikh; Mary McFarland; Lynn Pantages; Jeffrey B Madwed; Alexander J Szalai Journal: Arthritis Rheum Date: 2011-09
Authors: A Familian; A E Voskuyl; G J van Mierlo; H A Heijst; J W R Twisk; B A C Dijkmans; C E Hack Journal: Ann Rheum Dis Date: 2005-07 Impact factor: 19.103
Authors: Larissa F Marchi; Adriana B Paoliello-Paschoalato; Renê D R Oliveira; Ana Elisa C S Azzolini; Luciana M Kabeya; Eduardo A Donadi; Yara Maria Lucisano-Valim Journal: Rheumatol Int Date: 2018-02-20 Impact factor: 2.631
Authors: Ricardo G Espinola; Audrey Uknis; Irma M Sainz; Irma Isordia-Salas; Robin Pixley; Raul DeLa Cadena; Walter Long; Alexis Agelan; John Gaughan; Albert Adam; Robert W Colman Journal: Am J Pathol Date: 2004-09 Impact factor: 4.307
Authors: Eleonora Ballanti; Carlo Perricone; Elisabetta Greco; Marta Ballanti; Gioia Di Muzio; Maria Sole Chimenti; Roberto Perricone Journal: Immunol Res Date: 2013-07 Impact factor: 2.829
Authors: G Vaudo; S Marchesi; R Gerli; R Allegrucci; A Giordano; D Siepi; M Pirro; Y Shoenfeld; G Schillaci; E Mannarino Journal: Ann Rheum Dis Date: 2004-01 Impact factor: 19.103
Authors: Niubel Diaz Padilla; Wim K Bleeker; Yvonne Lubbers; Gemma M M Rigter; Gerard J Van Mierlo; Mohamed R Daha; C Erik Hack Journal: Immunology Date: 2003-08 Impact factor: 7.397