Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. 832

"Soluble liver antigen" (SLA) has been reported to be an infrequent but in certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18 as major antigenic components. Using precharacterized sera, we could confirm trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive protein. However, the reaction differed from that of cytokeratins 8 and 18 by molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and 18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver expression gene bank yielded no clones with sequence homology to cytokeratins. We conclude that reactivity in SLA positive sera is not mainly directed against cytokeratins 8/18 and recommend native antigen preparations for diagnostic use until the exact molecular nature of the 52 kD SLA antigen has been elucidated.
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PMID:Immunoreactivity to cytokeratin 8/18 in patients with soluble liver antigen (SLA) positive autoimmune hepatitis (AIH type 3) is not sufficient for diagnostic use. 1093 80

Keratin 8 and 18 (K8K18) mutations are found in patients with cryptogenic cirrhosis, but the role of keratin mutations in noncryptogenic cirrhosis and the incidence of keratin mutations in the general population are not known. We screened for K8K18 mutations in genomic DNA isolated from 314 liver explants of patients who primarily had noncryptogenic cirrhosis, and from 349 blood bank volunteers. Seven unique K8K18 mutations were found in 11 independent patients with biliary atresia, hepatitis BC, alcohol, primary biliary cirrhosis, and fulminant hepatitis. Seven of the 11 patients had mutations previously described in patients with cryptogenic cirrhosis: K8 Tyr-53 --> His, K8 Gly-61 --> Cys, and K18 His-127 --> Leu. The four remaining patients had mutations at one K8 and three other K18 new sites. Of the 349 blood bank control samples, only one contained the Tyr-53 --> His and one the Gly-61 --> Cys K8 mutations (P < 0.004 when comparing cirrhosis versus control groups). Two additional mutations were found in both the liver disease and blood bank groups and, hence, likely represent polymorphisms. Livers with keratin mutations had cytoplasmic filamentous deposits that were less frequent in livers without the mutations (P = 0.03). Therefore, K8K18 are likely susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease.
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PMID:Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies. 1272 28

Graft dysfunction mimicking autoimmune hepatitis rarely develops after liver transplantation for nonautoimmune disease. The mechanism(s) and causes of de novo autoimmune hepatitis are unknown. We examined autoantibodies serially in a patient with de novo autoimmune hepatitis and in patients without de novo autoimmune hepatitis after liver transplantation. Anticytokeratin 8/18 antibodies were detected in the first patient's sera after the onset of de novo autoimmune hepatitis, whereas other patients without de novo autoimmune hepatitis were seronegative throughout the follow-up period even with acute cellular rejection or other cause of liver dysfunction. In conclusion, the changes in cytokeratin 8/18 in hepatocytes might be one of the sources of pathogenesis of de novo autoimmune hepatitis after liver transplantation.
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PMID:Antibodies against cytokeratin 8/18 in a patient with de novo autoimmune hepatitis after living-donor liver transplantation. 1583 10