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Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis

Abstract : Background: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes. Methods: We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL) and the high C3 level group (C3≥120 mg/dL). Patient and renal survivals, association between C3 level and renal pathology were analysed. Results: Serum complement C3 concentration remained in the normal range [78-184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008) and lower eGFR (P = 0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046). No relationship between serum C4 and renal outcome was observed. Conclusion: A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.
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Contributor : jean-françois Augusto Connect in order to contact the contributor
Submitted on : Monday, January 31, 2022 - 4:23:59 PM
Last modification on : Wednesday, April 27, 2022 - 3:59:29 AM
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Jean-François Augusto, Virginie Langs, Julien Demiselle, Christian Lavigne, Benoit Brilland, et al.. Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis. PLoS ONE, Public Library of Science, 2021, 11 (7), pp.e0158871. ⟨10.1371/journal.pone.0158871⟩. ⟨inserm-03549837⟩



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