title: Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome.
abstract: BACKGROUND
  Abnormal control of the complement alternative pathway (CAP) (factor H, factor I and membrane cofactor protein (MCP) deficiencies) is a well established risk factor for the occurrence of haemolytic uraemic syndrome (HUS). In some instances, HUS may be associated with an unusual glomerulonephritis with isolated C3 deposits (glomerulonephritis C3). We determined whether HUS and glomerulonephritis C3 share common genetic susceptibility factors.
  
  
  METHODS
  We identified 19 patients with glomerulonephritis C3. We measured levels of circulating complement components, performed assays for the detection of C3 nephritic factor (C3NeF) and screened factor H, factor I and MCP coding genes for the presence of mutations.
  
  
  RESULTS
  Patients were divided in two groups based on renal pathology findings: group I (n = 13) had typical features of type I membranoproliferative glomerulonephritis (glomerulonephritis C3 with membranoproliferative glomerulonephritis (MPGN)) and group II (n = 6) was characterised by mesangial and epimembranous C3 deposits in the absence of mesangial proliferation (glomerulonephritis C3 without MPGN). Mutations in complement regulatory genes were detected in 4/6 patients with glomerulonephritis C3 without MPGN (heterozygous mutations in factor H gene (two patients) with low factor H antigenic level in one case, heterozygous mutations in factor I gene (two patients)) and in only 2/13 patients with glomerulonephritis C3 with MPGN (heterozygous mutations in factor H gene (one patient) and double heterozygous mutation in CD 46 gene (one patient)). In contrast, C3NeF was present in 5/13 patients with glomerulonephritis C3 with MPGN and in 2/6 patients with glomerulonephritis C3 without MPGN, one of whom had a factor H mutation.
  
  
  CONCLUSIONS
  HUS and glomerulonephritis C3 without MPGN share common genetic risk factors. Constitutional or acquired dysregulation of the CAP is probably associated with a wide spectrum of diseases, ranging from HUS to glomerulonephritis C3 with MPGN.
authors.affiliation: Department of Nephrology, Necker Hospital, Paris, France. aude.servais@psl.ap-hop-paris.fr
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: Moglie
authors.initials: M
authors.lastname: Lequintrec
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Jacques
authors.initials: J
authors.lastname: Blouin
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesavre
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003176:Complement C3 / Q000032:analysis*; D003178:Complement C3 Nephritic Factor / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis / Q000235:genetics; D003170:Complement Pathway, Alternative / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics; D050527:Mesangial Cells / Q000737:chemistry / Q000648:ultrastructure; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C497857:CD46 protein, human; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D051916:Membrane Cofactor Protein; D017242:Complement Factor H; D005340:Fibrinogen