Autoantibodies to Isolated Human Hepatocyte Plasma Membranes in Chronic Active Hepatitis. Ii. Specificity of Antibodies

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Abstract
The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one–dimensional immunoblotting. Sera from 12 patients with “classical” autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially “pathological.” In particular, one band with and apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver–specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented “natural” autoantibodies. Anti–human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G, M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human–specific polypeptides. The majority of anti–human hepatocyte plasma membranes appeared to be organ–specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess and array of liver–specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes. Those with highest affinity, avidity and serum titer (for example the 60 kD band) hold the greatest potential in future studies to define the candidate target autoantigen(s) involved in the pathogenesis of autoimmune chronic active hepatitis.(HEPATOLOGY 1990; 11:613:621.)