Detection of liver-kidney microsomal autoantibodies by radioimmunoassay and their relation to anti-mitochondrial antibodies in inflammatory liver diseases.

A radioimmunoassay (RIA) was developed for the detection of liver-kidney microsomal (LKM) autoantibodies. These were detected in four of 62 patients with HBsAg negative chronic active hepatitis (CAH) and in one patient with mixed connective tissue disease (MCTD). LKM antibodies were not detected in other hepatic and non-hepatic diseases. Other autoantibodies, especially anti-mitochondrial ones, do not react in this assay system. Sera positive for LKM antibodies by RIA showed a cytoplasmic staining of hepatocytes and proximal renal tubules by immunofluorescence. The LKM antigen was detected by RIA in microsomes prepared from rat liver, kidney, stomach, heart, lung, and skeletal muscle. It was destroyed after treatment with trypsin and chymotrypsin, but preserved after treatment with RNAase, DNAase and neuraminidase. Upon centrifugation of purified rat liver microsomes in CsCl gradient, LKM reactivity was detected at a density of 1.20 g/ml. In addition, the M2 antigen of the inner mitochondrial membrane specific for primary biliary cirrhosis (PBC) was localized at 1.28 g/ml in these density gradient fractions. The LKM antigen could not be solubilized. The presence of LKM antibodies characterizes a distinct subgroup of HBsAg negative CAH; they do not occur in PBC.