Nuclear envelope protein autoantibodies in primary biliary cirrhosis

A subset of patients with primary biliary cirrhosis (PBC) have autoantibodies directed against nuclear envelope proteins. The major autoantigen is gp210, a 210 kilodalton (kD) transmembrane protein of the nuclear pore complex, that is recognized by antibodies in approximately 25% of patients. The predominant epitope in gp210 that is recognized by most of the autoantibodies is a 15 amino acid stretch in the cytoplasmic, carboxyl-terminal domain of the protein. Gp210 autoantibodies are specific for PBC, as are the less frequent autoantibodies directed against LBR, a transmembrane protein of the inner nuclear membrane. Although autoantibodies against nuclear lamins, abundant intermediate filament proteins associated with the inner nuclear membrane, may be found in PBC, they are not specific for this disease. Nuclear envelope protein autoantibodies are also present in some patients without detectable antimitochondrial antibodies and may be of particular utility in diagnosing individuals with atypical presentations of PBC.