AUTOANTIBODIES FROM PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS RECOGNIZEA REGION WITHIN THE NUCLEOPLASMIC DOMAIN OF INNER NUCLEAR-MEMBRANE PROTEIN LBR

Autoantibodies from rare patients with primary biliary cirrhosis (PBC) recognize LBR, or lamin B receptor, an integral membrane protein of t he inner nuclear membrane. Human LBR has a nucleoplasmic, amino-termin al domain of 208 amino acids followed by a carboxyl-terminal domain wi th eight putative transmembrane segments. Autoantibodies against LBR f rom four patients with PBC recognized the nucleoplasmic, amino termina l domain but not the carboxyl-terminal domain. Immunoblotting of small er fusion proteins demonstrated that these autoantibodies recognized a conformational epitope(s) contained within the stretch of amino acids hom 1 to 60, These results, combined with those of previous studies, show that autoepitopes of nuclear membrane proteins are located within their nucleocytoplasmic domains and that autoantibodies hom patients with PBC predominantly react with one domain of a protein antigen, Thi s work also provides further characterization of anti-LBR antibodies t hat have found utility as reagents in cell biology research.