title: Membranoproliferative glomerulonephritis with C3NeF and genetic complement dysregulation.
abstract: The development of membranoproliferative glomerulonephritis (MPGN) is associated with uncontrolled activation of the complement alternative pathway. This dysregulation is related either to C3 nephritic factor (C3NeF), an auto-antibody directed against the alternative C3 convertase, or to homozygous loss-of-function mutation of the complement regulatory protein factor H. Heterozygous mutations in the genes coding for factor H, or for the other alternative pathway inhibitory proteins factor I and membrane cofactor protein, have recently been identified in a small number of patients with MPGN with exclusive C3 deposits. We report three hypocomplementemic children with dense deposit disease (n=1) or immune-complex-mediated MPGN type I (n=2), associated with both C3NeF activity and heterozygous mutation of factor H or factor I. These observations highlight the possible combination of genetic and acquired defect in complement control in various subtypes of MPGN, a finding that may influence the treatment strategy in some patients.
authors.affiliation: Pediatric Nephrology Department, Université Paris 7, Hôpital Robert Debré, Paris, France. valerie.leroy@unige.ch
authors.forename: Valérie
authors.initials: V
authors.lastname: Leroy
authors.forename: Véronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudouin
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Macher
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003178:Complement C3 Nephritic Factor / Q000032:analysis*; D017242:Complement Factor H / Q000235:genetics; D017244:Complement Factor I / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D009154:Mutation; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C493495:CFH protein, human; D003178:Complement C3 Nephritic Factor; D007166:Immunosuppressive Agents; D017242:Complement Factor H; C493611:CFI protein, human; D017244:Complement Factor I