Hepatitis B virus causes mixed cryoglobulinaemia by driving clonal expansion of innate B-cells producing a VH1-69-encoded antibody
Visentini, M.; Pascolini, S.; Mitrevski, M.; Marrapodi, R.; Del Padre, M.; Todi, L.; Camponeschi, A.; Axiotis, E.; Carlesimo, M.; De Santis, A.; Fiorilli, M.; Casato, M.
Clinical and Experimental Rheumatology 34(3 Suppl 97: S28-S32
2016
ISSN/ISBN: 0392-856X PMID: 26811981 Document Number: 689430
To investigate the expression of a VH1-69-encoded idiotype, and the phenotypic and functional features of monoclonal B-cells from patients with type II mixed cryoglobulinaemia (MC) secondary to chronic hepatitis B virus (HBV) infection. B-cell immunophenotype and expression of a VH1-69-encoded idiotype were investigated by flow cytometry. B-cell proliferative responses to stimuli were investigated by the CFSE dilution assay. Two out of five patients with chronic HBV studied had massive monoclonal expansion of VH1-69-expressing B-cells. These cells had the peculiar CD21(low) phenotype and low responsiveness to stimuli typical of the VH1-69-expressing B-cells commonly expanded in MC secondary to hepatitis C virus (HCV) infection. In both patients, anti-HBV therapy led to the regression of MC and of VH1-69+ B-cell expansion. VH1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including HCV E2, influenza A virus haemagglutinin and HIV gp41/gp120, and may serve as innate first line antiviral defense. Thus, like HCV, HBV may cause MC by protracted antigenic stimulation of VH1-69-expressing B-cells.