title: Streptococcal infection as possible trigger for dense deposit disease (C3 glomerulopathy).
abstract: Dense deposit disease (DDD, formerly known as membranoproliferative glomerulonephritis (MPGN) type II) is a subtype of C3 glomerulopathy (C3G). Electron-dense deposits in the glomerular basement membrane characterize this glomerulonephritis. DDD typically presents with a nephritic syndrome that progresses to end-stage renal failure in 50 % of patients despite treatment. The pathogenic basis of DDD is uncontrolled activation of the alternative complement cascade although the potential triggering events that precipitate the development of complement dysregulation are typically unknown. There are isolated reports of an apparent association between streptococcal infection and DDD, as well as with MPGN types I and III. However, this association has not been deemed compelling, perhaps because so few cases have been reported or because of a current lack of evidence for a plausible hypothesis to connect a streptococcal infection with subsequent disease. In this report, we describe two patients with DDD who definitely had an antecedent streptococcal infection with the phenotype of acute post-streptococcal glomerulonephritis and whose initial kidney biopsy findings on light microscopy were indistinguishable from acute post-streptococcal glomerulonephritis. These patients had additional points of interest: recurrence of gross hematuria with recurrent streptococcal infections, slowly progressive course, persistently low serum C3 concentration, positive C3 nephritic factor, and positive risk alleles in the complement factor H (CFH) gene.
  
  
  CONCLUSIONS
  We suggest that streptococcal infection may trigger DDD in individuals genetically predisposed by virtue of a disorder in complement regulation.
authors.affiliation: General Pediatrics, Children's Hospital of Philadelphia, 34th Street and Civic Center Blvd, Philadelphia, PA, 19104, USA, pupaj@email.chop.edu.
authors.forename: Julianne
authors.initials: J
authors.lastname: Prasto
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Kaplan
authors.forename: Pierre
authors.initials: P
authors.lastname: Russo
authors.forename: Elaine
authors.initials: E
authors.lastname: Chan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Kevin E C
authors.initials: KE
authors.lastname: Meyers
mesh_terms: D002648:Child; D003176:Complement C3 / Q000032:analysis; D003178:Complement C3 Nephritic Factor / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D010641:Phenotype; D013290:Streptococcal Infections / Q000150:complications*
chemical_list: C493495:CFH protein, human; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D017242:Complement Factor H