HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations

V. De Re, D. Sansonno, M. P. Simula, L. Caggiari, D. Gasparotto, M. Fabris, F. A. Tucci, V. Racanelli, R. Talamini, M. Campagnolo, S. Geremia, F. Dammacco, S. De Vita

Research output: Contribution to journalArticlepeer-review


We demonstrate that in three cases of MC (two with immunocytoma), the IgM-RF+ component of their cryoprecipitated represents the circulating counterpart of the B-cell receptor (BCR) of the monoclonal overexpanded B-cell population. These IgMs were isolated and used to demonstrate a crossreactivity against both hepatitis C virus (HCV) NS3 antigen and the Fc portion of IgG. Epitopes were identified in a fraction of exemplary samples by using epitope excision approach (NS31250-1334 and IgG Fc345-355). The same phenomenon of crossreactivity has been shown to occur in vivo after immunization of a mouse with the NS31251-1270 peptide. To verify if the same reaction was also present in MC samples characterized by an oligo/polyclonal B-cell proliferation, IgM crossreactivity was tested in 14 additional samples. Five out of the 14 were reactive against HCV NS3 and 11 out of 14 were reactive against IgG-Fc peptide. The data support the role of HCV NS3 antigen in a subset of patients with MC, whereas the high frequency of the IgG-Fc epitope suggests that these B cells originate from precursors strongly selected for auto-IgG specificity. We suggest that engagement of specific BCRs by NS3 (or NS3-immunocomplex) antigen could explain the prevalence of IgM cryoglobulins in these patients.

Original languageEnglish
Pages (from-to)1145-1154
Number of pages10
Issue number6
Publication statusPublished - Jun 2006


  • Hepatitis C virus
  • Lymphoproliferative diseases
  • Rheumatoid factor

ASJC Scopus subject areas

  • Hematology
  • Cancer Research


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