Methodology and significance of the detection of liver-kidney-microsomal (lkm) autoantibodies in autoimmune-type chronic active hepatitis

Abstract

Liver-kidney-microsomal (LKM) autoantibodies are diagnostic markers for a subgroup of HBsAg-negative chronic active hepatitis, presumably owing to autoimmunity. They were originally detected by indirect immunofluorescence and can now be evaluated by radioimmunoassay, enzyme-linked immunosorbent assay, and immunoblotting. In immunoblotting LKM-positive sera react strongly with a 50-kilodalton (KD) polypeptide band of microsomes. In immunoelectron microscopy, LKM-positive sera show a binding with membranes of the endoplasmic reticulum. The LKM antigen was further identified on various isoenzymes of cytochrome P-450. Immunofluorescence is still the method of choice for screening sera routinely. However, cytplasmic antigen-antibody systems often can hardly be distinguished by this method. A specific radioimmunoassay and an enzyme-linked immunosorbent assay can differentiate the various autoantibodies against cytoplasmic antigens. Immunoblotting and immunoelectron microscopy are specific tools for the characterization of the target antigens on an ultrastructural or molecular level. So far they have no use in routine testing of sera. However, since LKM antigen was localized on isozymes of cytochrome P-450, this subgroup of CAH might turn out to be a drug-induced autoimmune liver disease. Clinically, these patients are characterized by chronic active hepatitis or cirrhosis in liver histology, a slight predominance of females, low IgA immunoglobulin levels, and an often rapidly progressing disease. Patients can be treated with immunosuppressive drugs. However, controlled therapeutical trials are missing. Furthermore, an immunogenetic background still has to be proven for this autoimmune liver disease.