Virus-induced anti-asialoglycoprotein receptor autoimmunity in experimental hepadnaviral hepatitis.

Abstract

The relationship between hepatitis virus invasion and emergence of liver-specific autoantibodies against asialoglycoprotein receptor (anti-ASGPR) and the occurrence patterns, prognostic value, and specificity of these autoantibodies toward polypeptides of host ASGPR were investigated in experimental viral hepatitis in the woodchuck system. Sequential sera (n = 231) obtained before and after inoculation with woodchuck hepatitis virus (WHV) from animals which resolved acute infection (n = 7) or developed chronic hepatitis (n = 6) were tested for anti-ASGPR using radio and enzyme-immunodetection assays. In addition, the outcome of WHV hepatitis was analyzed in 30 other woodchucks whose preinoculation sera were tested for anti-ASGPR. The receptor subunit specificity of virus-induced anti-ASGPR was determined by Western blotting and compared with that of anti-ASGPR raised in woodchucks challenged with a heterologous (rabbit) receptor. The results revealed that WHV infection triggered anti-ASGPR in all except one of the initially autoantibody nonreactive animals (eight of nine; 89.9%). Once induced, anti-ASGPR were detectable throughout the entire follow-up independent of histological severity of liver damage or the outcome of hepatitis. In healthy WHV-naive woodchucks, anti-ASGPR occurred at low titers in approximately one third of the animals. Importantly, woodchucks reactive for anti-ASGPR before WHV inoculation developed chronic hepatitis with a significantly greater frequency (55.5%) than those autoantibody negative (15.6%; P < .05). In contrast to anti-ASGPR elicited by immunization with a heterologous receptor, which initially recognized only the ASGPR 40-kd polypeptide, anti-ASGPR emerging after virus invasion reacted with both the ASGPR 40- and 47-kd subunits from the moment of their appearance. This study provides the first direct evidence that hepatitis virus in the natural host triggers autoantibodies against a unique hepatocyte antigen and shows that anti-ASGPR autoimmunity existing before virus infection is associated with a high rate of progression to chronic disease in experimental hepadnaviral hepatitis.

• Authors: J Diao, T I Michalak
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 25 Issue 3 Pg. 689-96 (Mar 1997) ISSN: 0270-9139 [Print] United States
• PMID: 9049220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asialoglycoprotein Receptor
• Autoantibodies
• Receptors, Cell Surface

Topics

• Animals
• Asialoglycoprotein Receptor
• Autoantibodies (blood)
• Blotting, Western
• Cross Reactions (immunology)
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Hepatitis B Virus, Woodchuck (immunology)
• Marmota
• Receptors, Cell Surface (immunology)