Hepatitis C virus (HCV)-driven stimulation of subfamily-restricted natural IgM antibodies in mixed cryoglobulinemia

Mario Perotti, Nadia Ghidoli, Raffaele Altara, Roberta A. Diotti, Nicola Clementi, Donata De Marco, Monica Sassi, Massimo Clementi, Roberto Burioni, Nicasio Mancini

Research output: Contribution to journalArticlepeer-review


Hepatitis C virus (HCV) infection has been closely related to mixed cryoglobulinemia (MC). During HCV infection, cryoglobulins derive from the restricted expression of few germline genes as VH1-69, a subfamily highly represented in anti-HCV humoral response. Little is known about the self-reacting IgM component of the cryoprecipitate. In the present study, the IgM/K repertoire of an HCV-infected cryoglobulinemic patient was dissected by phage-display on well-characterized anti-HCV/E2 VH1-69-derived monoclonal IgG1/Κ Fab fragments cloned from the same patient. All selected IgM clones were shown to react with the anti-HCV/E2 antibodies belonging to VH1-69 subfamily. More than 60% of selected clones showed a bias in VH gene usage, restricted to two VH subfamilies frequently described in autoimmune manifestations (VH3-23; VH3-21). Moreover, all selected clones showed an high similarity (> 98.5%) to germline genes evidencing their natural origin. A possible hypothesis is that clones belonging to some subfamilies are naturally prone to react against other VH gene subfamilies, as VH 1-69. An antigen-driven stimulation of these subfamilies, and their overexpression as in HCV infection, could lead to a breaking of humoral homeostatic balance exposing the patients to the risk of developing autoimmune disorders.

Original languageEnglish
Pages (from-to)468-472
Number of pages5
JournalAutoimmunity Reviews
Issue number6
Publication statusPublished - Jun 2008


  • Autoimmunity
  • Cryoglobulinemia
  • HCV
  • Lymphoma

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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