title: B cell activating factor (BAFF) in the natural history of chronic hepatitis C virus liver disease and mixed cryoglobulinaemia.
abstract: B cell activating factor (BAFF) plays a crucial role in the process of development, maturation and activation of B lymphocytes. Chronic hepatitis C virus (HCV) infection is characterized by multiple B cell disorders. It is a major cause of type II mixed cryoglobulinaemia (MC). We measured serum BAFF levels in several clinical situations to elucidate the potential role of BAFF in chronic HCV infection. We used a commercially available solid phase enzyme-linked immunosorbent assay. We estimated serum BAFF in stored sera from uninfected controls (n = 8), patients with chronic hepatitis B virus infection HBV (n = 5) and chronic HCV infection with (n = 16) and without mixed cryoglobulinaemia (n = 14). In two patients with HCV and MC we correlated BAFF with HCV RNA after pegylated interferon (peg-I). We correlated serum BAFF levels at baseline and at 12 weeks with treatment response: sustained virological response SVR (n = 5), non-responders (n = 6) and relapsers (n = 2). Finally, we estimated BAFF levels after complete depletion of B cells with rituximab in patients with chronic HCV with MC (n = 3). Serum levels of BAFF were increased in chronic HCV with MC, but not in chronic HBV infection, suggesting an association between BAFF and cryoglobulinaemia. Peg-I increased BAFF levels in serum and this paralleled HCV RNA very closely. Serum BAFF levels at week 12 of therapy with peg-I and R were significantly higher in responders than non-responders. Finally, B cell depletion was associated with markedly increased levels of BAFF.
authors.affiliation: Center for the Study of Hepatitis C, Weill Medical College Cornell University, New York, NY, USA. glakebak@bidmc.harvard.edu
authors.forename: G
authors.initials: G
authors.lastname: Lake-Bakaar
authors.forename: I
authors.initials: I
authors.lastname: Jacobson
authors.forename: A
authors.initials: A
authors.lastname: Talal
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000097:blood* / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003449:Cryoglobulinemia / Q000097:blood / Q000276:immunology* / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006509:Hepatitis B / Q000097:blood / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; D011092:Polyethylene Glycols; D000069283:Rituximab; C417083:peginterferon alfa-2b