The pathophysiology of HCV induced B-cell clonal disorders.
Hepatitis C virus (HCV) has been shown in epidemiologic studies to be associated with immune system disorders. Primarily disorders that stem from B-cell regulatory control disturbance, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL). The causative role of HCV in these disorders is supported by the response to anti-viral treatment. The understanding of the pathophysiological process leading from HCV infection to B-cell clonal expansion has improved significantly. Data supports an antigen-driven indirect stimulation of clonal expansion model, leading from oligoclonal to monoclonal expansion and in some instances to frank malignancy. HCV-E2 antigen has been suggested as a candidate antigen as well as NS3. Binding of the B-cell receptor by viral antigens coupled with direct binding of CD-81 by HCV-E2 has been shown to provide a strong proliferative signal. Additional regulatory elements are also affected in HCV-related B-cell clonal expansion, including the Fas and BLyS signaling mechanisms. Finally, genetic events such as bcl-2 rearrangement may also be involved in clonal expansion. In this review, evidence linking HCV with MC and NHL, as well as known events in the pathophysiological process are described.
Landau
Dan-Avi
DA
Université Pierre et Marie Curie-Paris 6, CNRS, UMR 7087, Paris, F-75013 France.
Saadoun
David
D
Calabrese
Leonard H
LH
Cacoub
Patrice
P
D001402:B-Lymphocytes / Q000276:immunology*; D003449:Cryoglobulinemia / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000821:virology