Autoantibody pattern in a woodchuck model of hepatitis B.
Spectrum, dynamics, and immunoglobulin class of the non-organ specific autoantibodies were investigated in 646 sequential sera from 18 woodchucks with experimental woodchuck hepatitis virus (WHV) infection and in 8 naturally infected chronic carriers of the virus. Among examined WHV carriers, 8 animals developed hepatocellular carcinoma. The sera were tested by indirect immunofluorescence for autoantibodies against smooth muscle (SMA), nuclei (ANA), brush border of proximal renal tubuli (ABBA), and mitochondria (AMA). Analysis revealed that inoculation with WHV was followed by the appearance and/or meaningful elevation of the titre of SMA in IgG class. In all 18 experimentally infected woodchucks, the autoantibody rise preceded the appearance of viral serologic markers (WHsAg and/or WHeAg) by 1 to 4 weeks (mean +/- SD = 2.5 +/- 1.5 weeks). Once induced, SMA remained steadily detectable achieving the peak titre value around week 12 postinoculation. The SMA dynamics did not parallel with the fluctuation of the virus serologic markers and they were similar both in animals who recovered from acute episodes and in those who progressed to chronic infection. In chronic carriers, contrasted to acute infection, fluctuation of SMA titre even to undetectable levels and frequent parallel rises and falls of SMA, ANA, and ABBA titres were observed. A different pattern was found in all three chronic carriers who acquired infection from mothers. In this group, high and relatively stable autoantibody levels were detected. Development of hepatocellular carcinoma was not associated with any specific autoantibody pattern. This study revealed that WHV invasion undoubtedly induces non-organ specific autoimmune response.(ABSTRACT TRUNCATED AT 250 WORDS)
Dzwonkowski
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Liver Research Laboratory, Faculty of Medicine, Memorial University of Newfoundland, St. John's.
Michalak
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D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015613:Hepadnaviridae / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000276:immunology*; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000382:microbiology; D007684:Kidney Tubules / Q000276:immunology; D008392:Marmota; D008928:Mitochondria / Q000276:immunology; D009130:Muscle, Smooth / Q000276:immunology
D000974:Antibodies, Antinuclear; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D006508:Hepatitis Antibodies