title: 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.
  
  
  CONCLUSIONS
  A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.
authors.affiliation: LUNAM Université, Angers, France.|Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Augusto
authors.affiliation: Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Langs
authors.affiliation: Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Demiselle
authors.affiliation: Université Angers, CHU Angers, Service de Médecine Interne, Angers, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Lavigne
authors.affiliation: Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Brilland
authors.affiliation: Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Duveau
authors.affiliation: LUNAM Université, Angers, France.|Université d'Angers, CHU Angers, Laboratoire d'Immunologie, Angers, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Poli
authors.affiliation: LUNAM Université, Angers, France.|Université d'Angers, CHU Angers, Laboratoire d'Immunologie, Angers, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chevailler
authors.affiliation: Université Angers, CHU Angers, Département de Pathologie Cellulaire et Tissulaire, Angers, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Croue
authors.affiliation: Diaverum Dialysis Center, Angers, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Tollis
authors.affiliation: Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Johnny
authors.initials: J
authors.lastname: Sayegh
authors.affiliation: LUNAM Université, Angers, France.|Université Angers, CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Angers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Subra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D003176:Complement C3 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D003176:Complement C3