학술논문

HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations.
Document Type
Article
Source
Leukemia (08876924). Jun2006, Vol. 20 Issue 6, p1145-1154. 10p. 1 Chart, 5 Graphs.
Subject
*LYMPHOPROLIFERATIVE disorders
*CELL proliferation
*B cells
*CRYOGLOBULINEMIA
*BLOOD protein disorders
*HEPATITIS C virus
*FLAVIVIRUSES
Language
ISSN
0887-6924
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 patientsLeukemia (2006) 20, 1145–1154. doi:10.1038/sj.leu.2404201; published online 13 April 2006 [ABSTRACT FROM AUTHOR]