The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha.
OBJECTIVE
Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients.


METHODS
Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes.


RESULTS
Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome.


CONCLUSIONS
Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.
I. Department of Internal Medicine, Johannes-Gutenberg University Mainz, Germany.
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Löhr
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Elste
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Dienes
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Michel
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Braun
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Meyer zum Büschenfelde
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Gerken
D000328:Adult; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000032:analysis / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins
D000936:Antigen-Antibody Complex; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins