Abstract
BackgroundRecent 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.MethodsWe 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.ResultsSerum 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.ConclusionA Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.
Highlights
Recent studies have demonstrated the key role of the complement alternative pathway in the pathophysiology of experimental Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)
A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are life threatening autoimmune diseases characterised by necrotising inflammation of small to medium-sized vessels [1,2,3] and the detection of ANCAs in serum
Summary
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are life threatening autoimmune diseases characterised by necrotising inflammation of small to medium-sized vessels [1,2,3] and the detection of ANCAs in serum. The understanding of human AAV pathophysiology has greatly benefited from discoveries made in murine MPO-ANCA vasculitis models [7, 8] In this model, MPO-ANCAs are induced in MPO-deficient mice and transferred into wild-type mice, resulting in the development of NCGN. MPO-ANCAs are induced in MPO-deficient mice and transferred into wild-type mice, resulting in the development of NCGN Using this model, Xiao et al were the first to demonstrate that the complement alternative pathway (cAP) plays a crucial role in experimental vasculitis [9]. Xiao et al were the first to demonstrate that the complement alternative pathway (cAP) plays a crucial role in experimental vasculitis [9] They applied the MPO-ANCA vasculitis model to mice decomplemented with cobra venom factor, and to C5-, C4- and Factor B deficient mice. We analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes
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