Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis.
The isolation of a marker antigen from rat liver and pancreas tissue, which reacts with antibodies in a subtype of autoimmune hepatitis by complement fixation test, enzyme-linked immunosorbent assay and Western blot, is described. The liver-pancreas antigen could be detected in tissue from different human or animal organs, but liver and pancreas yielded the highest activity. A highly specific antigen fraction was obtained by gel filtration and ion exchange chromatography with a 100,000 g supernatant from rat liver tissue, and this preparation was shown to be devoid of nuclear, mitochondrial and microsomal antigens and cytokeratin 8 and 18, as demonstrated by appropriate marker antibodies. These data and absorption studies with cell organelles indicate that liver-pancreas antigen is a cytosolic protein. By Western blotting, two major epitopes at molecular weights 52 kD and 48 kD could be visualized. Sera from 175 patients previously shown to have high complement-fixing activity to a nonpurified liver-pancreas antigen fraction were further analyzed. All were positive by enzyme-linked immunosorbent assay with the purified liver-pancreas antigen fractions, and 111 were also positive by Western blot. Eighty-six sera reacted with the 52-kD determinant, 33 with the 48-kD determinant and 2 with both determinants. In 117 of the 175 patients, antibody to liver-pancreas antigen was associated with other autoantibodies known to characterize subgroups of autoimmune hepatitis. Thus 19 patients had antibodies to nuclei and 96 to actin but none to liver-kidney microsomes, hereby suggesting that antibody to liver-pancreas antigen may define another subgroup of autoimmune hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Stechemesser
E
E
Department of Internal Medicine, University of Tübingen, Germany.
Klein
R
R
Berg
P A
PA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015153:Blotting, Western; D002417:Cattle; D002648:Child; D003165:Complement System Proteins / Q000276:immunology; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006521:Hepatitis, Chronic / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology*; D011817:Rabbits; D013045:Species Specificity; D013552:Swine
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D003165:Complement System Proteins