6533b834fe1ef96bd129d5ac

RESEARCH PRODUCT

Nature of autoantigens and autoantibodies in autoimmune hepatitis

subject

description

Autoimmune chronic active hepatitis (AI-CAH) is characterized by young age at onset, predominance of females, hypergammaglobulinemia, response to immunosuppressive treatment and characteristic circulating autoantibodies. This clinical syndrome was first described by Waldenstr6m in 1950 [47]. Later the association of autoimmune hepatitis with antinuclear antibodies (ANA) lead to the term "lupoid hepatitis" [19]. Additional autoantibodies have been described [21]. At least three subgroups of AI-CAH can be distinguished serologically and clinically [28]. As diagnostic tools, autoantibodies help to further differentiate the heterogeneous group of hepatitis B virus (HBV) surface antigen (HBsAg)-negative CAH. This is clinically relevant since patients with AI-CAH profit from immunosuppression, while this treatment may be harmful for patients with virus-induced liver disease [41]. Autoantibodies are not only useful as diagnostic markers, but may become tools for further elucidating the pathogenesis of liver disease in which a loss of tolerance against autologous liver tissue is regarded as a major pathogenetic mechanism. Candidate autoantibodies with pathogenetic relevance should be disease specific, autoantigens should be expressed on the cell surface or should have a function with significance for cell integrity. Although the main autoimmune liver diseases are associated with characteristic autoantibodies, tissue inf'fltrating T lymphocytes are regarded as primary candidates to mediate tissue destruction. Despite the fact that tissue infiltrating T lymphocytes can be isolated, cloned and studied in vitro, their antigen specificity in autoimmune liver diseases remains unknown. Precise identification and characterization of autoantigens recognized by autoantibodies will not only provide clinicians with diagnostic reagents, but might also help to elucidate further the pathogenesis of these inflammatory liver diseases.