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Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome
  1. Aude Servais1,
  2. Véronique Frémeaux-Bacchi2,
  3. Moglie Lequintrec1,
  4. Rémi Salomon1,
  5. Jacques Blouin2,
  6. Bertrand Knebelmann1,
  7. Jean-Pierre Grünfeld1,
  8. Philippe Lesavre1,
  9. Laure-Hélène Noël3,
  10. Fadi Fakhouri1
  1. 1Department of Nephrology, Necker Hospital, Paris, France
  2. 2Department of Clinical Immunology, Georges Pompidon European Hospital, Paris, France
  3. 3Department of Pathology, Necker Hospital, Paris, France
  1. Correspondence to:
 Dr Aude Servais
 Service de Néphrologie adultes, Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France; aude.servais{at}psl.ap-hop-paris.fr

Abstract

Introduction: 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.

Conclusion: 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.

  • C3NeF, C3 nephritic factor
  • CAP, complement alternative pathway
  • HUS, haemolytic uraemic syndrome
  • MCP, membrane cofactor protein
  • MPGN, membranoproliferative glomerulonephritis

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Footnotes

  • Published Online First 3 October 2006

  • Competing interests: None.

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