title: HCV replication in mononuclear cells stimulates anti-HCV-secreting B cells and reflects nonresponsiveness to interferon-alpha.
abstract: Recently, it was demonstrated in chronic hepatitis C that the release of IgG and IgM anti-HCV antibodies by mononuclear cells (PBMCs) correlated with inflammatory activity, HCV persistence in serum, and negative outcome from antiviral therapy. Thus, persistent antigenic stimulation of the antibody-secreting B cells has been suggested. In this study, PBMCs were derived from 13 patients with chronic hepatitis C. Nucleic acids were extracted by the guanidine-thiocyanate-method, and plus- and minus-stranded HCV-RNAs were determined using primers from the 5'-untranslated region of HCV. Simultaneously, unstimulated PBMCs were cultured for 8 days and anti-HCV antibodies were detected in the supernatants by EIA and RIBA. Seven patients (53.8%) had both plus- and minus-stranded HCV-RNA in PBMCs, while anti-HCV antibodies were secreted in vitro. One of 2 patients with plus- but not minus-stranded HCV-RNA in PBMCs was anti-HCV positive in vitro, whereas 4 patients without HCV-infected PBMCs were anti-HCV negative in vitro. Eight patients received antiviral therapy with interferon-alpha 2b. Four nonresponders and 1 partial responder had plus- and minus-stranded HCV-RNA in PBMCs and anti-HCV secretion in vitro. On the other hand, 2 complete responders and another partial responder showed neither HCV infection of PBMCs nor anti-HCV secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: First Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, Germany.
authors.forename: H F
authors.initials: HF
authors.lastname: Löhr
authors.forename: B
authors.initials: B
authors.lastname: Goergen
authors.forename: K H
authors.initials: KH
authors.lastname: Meyer zum Büschenfelde
authors.forename: G
authors.initials: G
authors.lastname: Gerken
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D002908:Chronic Disease; D017931:DNA Primers; D005260:Female; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology* / Q000628:therapy / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins