title: Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection.
abstract: Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5(+) subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5(+) B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5(+) B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5(+) population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5(+) peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.
authors.affiliation: Department of Internal Medicine A Institute of Clinical Immunology, Bnai Zion Medical Center, Haifa, Israel. zuckerman@b-zion.org.il
authors.forename: Eli
authors.initials: E
authors.lastname: Zuckerman
authors.forename: Aharon
authors.initials: A
authors.lastname: Kessel
authors.forename: Gleb
authors.initials: G
authors.lastname: Slobodin
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Daniel
authors.initials: D
authors.lastname: Yeshurun
authors.forename: Elias
authors.initials: E
authors.lastname: Toubi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000737:chemistry*; D018956:CD5 Antigens / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; D018956:CD5 Antigens; C554798:CD81 protein, human; D016898:Interferon-alpha; D008565:Membrane Proteins; D012367:RNA, Viral; D060225:Tetraspanin 28; D012254:Ribavirin