AUTOANTIBODIES FROM PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS PREFERENTIALLY REACT WITH THE AMINO-TERMINAL DOMAIN OF NUCLEAR-PORE COMPLEX GLYCOPROTEIN GP210

Patients with primary biliary cirrhosis frequently develop autoantibod ies directed to gp210, a major glycoprotein of the nuclear pore comple x. This protein contains a large glycosylated cisternal domain, a sing le transmembrane segment, and a short cytoplasmic tail. It has been pr eviously shown that autoantibodies from primary biliary cirrhosis pati ents exclusively react with the cytoplasmic tail. We demonstrate that autoantibodies against gp210 recognize at least two different epitopes . 4 out of 12 anti-gp210 positive sera reacted with the fragment consi sting of the cytoplasmic tail, and 8 sera targeted a novel epitope loc ated within the large glycosylated lumenal domain. Moreover, our data prove that carbohydrate moieties are an essential part of this novel e pitope. We propose, therefore, that future screening assays should be performed with antigens possessing both epitopes to detect all sera wi th anti-gp210 specificity.