Molecular analysis of autoantigens in hepatitis D

In contrast to hepatitis B virus infection, autoimmunity is common in chronic hepatitis D. In 1983, microsomal autoantibodies were described that differ from the previously described liver-kidney microsomal (LKM)-1 and LKM-2 antibodies. Therefore, these were named LKM-3. In addition, autoantibodies against basal layer cells of rat forestomach (basal cell layer antibodies (BCLA)) and thymic stellate epithelial cells (stellate epithelial cell antibodies (SECA)), as well as thymic reticular (thymic reticular antibodies) and perithymocytic cells (perithymocytic cell antibodies), were reported to be specifically associated with hepatitis D. Antinuclear antibodies against nuclear membrane lamin C were also found to be specifically associated with chronic hepatitis D. A molecular identification of the nonnuclear antigens has not been achieved apart from the observation that BCLA and SECA both recognize an antigen of 46 kDa and that these antibodies are immunologically cross-reactive. After the identification of cytochrome P450 2D6 as the major LKM-1 antigen and cytochrome P450 2C9 as the LKM-2 antigen, family 1 uridine diphosphate-glucuronosyltransferases have been identified as the molecules expressing the major LKM-3 autoepitope. Future studies will have to assess the possible pathogenetic and diagnostic relevance of these autoantibodies. However, chronic hepatitis D seems to be a good clinical model for the study of virus-induced autoimmunity in man.