VIRAL INDUCTION OF AUTOIMMUNITY - MECHANISMS AND EXAMPLES IN HEPATOLOGY

Autoimmunity may be observed in chronic viral hepatitis, in particular hepatitis C and D., The hepatitis C virus (HCV) displays numerous int eractions with the immune system, Hepatitis C virus induces a number o f diseases of presumed autoimmune background, like mixed cryoglobulina emia, glomerulonephritis, panarthritis, arthritis thyroiditis and skin lesions, On the other hand a number of autoantibodies are observed du ring the course of hepatitis C, Of particular interest are liver/kidne y microsomal antibodies (LKM). Their occurrence in viral hepatitis may indicate an increased risk for treatment with interferons. LKM antibo dies in chronic hepatitis C recognize several autoepitopes differing f rom those in autoimmune hepatitis, Hepatitis C-associated LKM antibodi es are more heterogeneous, They recognize either conformational or sev eral distinct linear autoepitopes on cytochrome P450 2D6; they may als o react with other microsomal proteins, Apart from their molecular wei ght at 59 and 70 kDa these microsomal antigens are not yet identified, Another model of virus-induced autoimmunity in man is chronic hepatit is D which always requires coinfection with hepatitis B. Hepatitis D i s known to be associated with a number of autoantibodies, amongst them LKM-3. LKM-3 antibodies have recently been shown to react with protei ns of the UDP glucuronosyl-transferase family (UGT). The main antigen is an autoepitope expressed on exon 2-5 of family 1 UGTs. Some hepatit is D sera recognize a minor second epitope on family 2 UGTs., It is in teresting that hepatitis C patients recognize proteins of the cytochro me P450 family while hepatitis D sera react with UGTs., There seems to be little overlap between autoimmunity seen in hepatitis C and a as f ar as autoepitopes are concerned. LKM-3 antibodies against UGT 1 are a lso seen in a minority of patients with autoimmune hepatitis type 2. H owever, the autoimmune response against UGTs seen in autoimmune hepati tis differs from that observed in Viral hepatitis, Autoantibodies in a utoimmune liver disease are usually more homogenous and are directed a gainst precise linear epitopes. Autoepitopes in autoimmune hepatitis u sually represent conserved regions of these proteins, the antibody usu ally is inhibitory and antibody titres are very high. In contrast, aut oantibodies in viral hepatitis are more heterogenous, recognize severa l linear and conformational epitopes; antibody titres are much lower. However, the major LKM autoantigen in chronic hepatitis C also is P450 2D6. Autoimmune hepatitis and autoimmunity in viral hepatitis must be distinguished clinically by all means due to the need for specific th erapeutic interventions. These liver diseases may serve as models to s tudy virus induced autoimmunity and autoimmune disease in man.