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Myeloma

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

Leukemia volume 20, pages 1145–1154 (2006)Cite this article

Abstract

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

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Acknowledgements

We thank Alessandra Marzotto for technical help and Luigina Mei for editorial assistence. Source of support: this study was supported by ‘Associazione Italiana per la Ricerca sul Cancro’ (AIRC), by grants from the Fondo Sanitario Nazionale-Ministero della salute-FSN 2003, Fondo regionale Friuli-Venezia-Giulia project LR 11/2003 and by Società Italiana di Reumatologia.

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Authors and Affiliations

  1. Division of Experimental Oncology I, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, Pordenone, Italy

    V De Re, M P Simula, L Caggiari, D Gasparotto & F A Tucci

  2. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy

    D Sansonno, F A Tucci, V Racanelli & F Dammacco

  3. Division of Rheumatology-DPMSC, University of Udine Medical School, Udine, Italy

    M Fabris & S De Vita

  4. Department of Pre-Clinical and Epidemiological Research, Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, Pordenone, Italy

    R Talamini

  5. Department of Chemical Sciences, Centre of Excellence in Biocrystallography, University of Trieste Chemistry, Trieste, Italy

    M Campagnolo & S Geremia

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Correspondence to V De Re.

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De Re, V., Sansonno, D., Simula, M. et al. HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations. Leukemia 20, 1145–1154 (2006). https://doi.org/10.1038/sj.leu.2404201

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