Reactivities and clinical relevance of antimitochondrial antibodies to four mitochondrial inner membrane proteins in sera of patients with primary biliary cirrhosis.

Antimitochondrial antibodies are characteristically detected in sera of patients with primary biliary cirrhosis. The antigens to which the antimitochondrial antibodies in primary biliary cirrhosis sera react have been located in the mitochondrial inner membrane. We have reported on four mitochondrial inner membrane proteins, extracted from beef heart, which reacted with antimitochondrial antibodies of primary biliary cirrhosis. These four proteins had molecular weights of 70, 54, 51 and 45 kd. Forty-six of the 50 PBC sera tested were positive with rat kidney and stomach specimens by the indirect immunofluorescent method. All sera of 50 primary biliary cirrhosis patients were positive with at least one and as many as four of the mitochondrial proteins extracted from beef heart using immunoblotting. Forty-seven primary biliary cirrhosis sera (94%) had IgG antibodies (antimitochondrial antibodies) to the antigen proteins, 43 patients (86%) IgM antimitochondrial antibodies and 38 patients (76%) IgA antimitochondrial antibodies. Seventy per cent of patients had antimitochondrial antibodies in all three immunoglobulin classes. In a few primary biliary cirrhosis sera, antimitochondrial antibodies were represented by only one class of immunoglobulin. The major antigenic proteins of mitochondrial inner membrane to which the antimitochondrial antibodies react were the 70 and 51 kd proteins. All primary biliary cirrhosis sera containing antibodies to the 54 and/or 45 kd proteins reacted with 70 kd as well. Patients with an elevation of serum bilirubin over 2 mg per dl were often found to produce antimitochondrial antibodies reactive with the 54 kd in addition to the 70 kd protein. No significant association was found between histological classifications and reactive patterns of antimitochondrial antibodies.