title: Membranoproliferative glomerulonephritis and mixed cryoglobulinemia after hepatitis C virus infection secondary to glomerular NS3 viral antigen deposits.
abstract: BACKGROUND
  We report on 3 cases of membranoproliferative glomerulonephritis associated with mixed cryoglobulin in patients with hepatitis C virus (HCV) antibodies but a negative blood viral load. These cases explore the pathogenesis of the renal disease.
  
  
  METHODS
  We searched for occult HCV infection in peripheral blood mononuclear cells, cryoprecipitate, bone marrow cells, and glomeruli using ultrasensitive PCR assays and immunohistochemistry. We also looked for infraclinical B cell lymphoma by computed tomodensitometry, bone marrow aspiration and biopsy, and lymphocyte typing.
  
  
  RESULTS
  By PCR assays, we did not evidence occult hepatitis C infection in peripheral blood mononuclear cells, bone marrow cells, or cryoprecipitates. In the only patient with available kidney specimen, we evidenced HCV-NS3 antigen in glomeruli. HCV-associated lymphoma was excluded, but mild polyclonal B lymphocytosis was present in the 3 patients. Remission occurred spontaneously in 1 patient, and in another patient it occurred after rituximab treatment. The third patient was lost to follow-up.
  
  
  CONCLUSIONS
  In patients with hepatitis C-negative viral load, membranoproliferative glomerulonephritis could be induced by the persistence of HCV antigen in the kidney but not in hematopoietic cells. Nonlymphomatous B cell proliferation may also be induced by chronic viral stimulation.
authors.affiliation: Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Marseille, France. stanislas.bataille@ap-hm.fr
authors.forename: Stanislas
authors.initials: S
authors.lastname: Bataille
authors.forename: Gilles
authors.initials: G
authors.lastname: Kaplanski
authors.forename: José
authors.initials: J
authors.lastname: Boucraut
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Claire
authors.initials: C
authors.lastname: Camus
authors.forename: Laurent
authors.initials: L
authors.lastname: Daniel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Burtey
authors.forename: Yvon
authors.initials: Y
authors.lastname: Berland
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000009:adverse effects* / Q000302:isolation & purification; D001402:B-Lymphocytes; D003449:Cryoglobulinemia / Q000276:immunology* / Q000821:virology; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008218:Lymphocytosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000956:Antigens, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases