title: Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D.
abstract: Patients with chronic hepatitis D often have liver-kidney microsomal antibodies type 3 (LKM-3). These antibodies react with several microsomal antigens that have a molecular weight of 55 KDa and an isoelectric point of about 8. We studied the molecular nature of the antigen and, by immunoscreening a human liver cDNA expression library with KM-3 sera, found that uridine diphosphate glucuronosyl transferases (UGT) appeared as candidate antigens. We confirmed the identity of UGT as an antigen by reacting the sera with recombinant rabbit liver UGT proteins. Some sera reacted with rabbit UGT-2 proteins, but UGT-1 proteins were more sensitive and specific in detecting LKM-3 autoantibodies in patient sera. Anti-UGT-1 antibodies were detected in all LKM-3 positive sera from patients with hepatitis D and 1 out of 11 patients with autoimmune hepatitis type 2. Sera from patients who had hepatitis B only did not react with UGT proteins. The UGT proteins are part of the phase II enzymes of drug metabolism and are the first such enzymes to be identified as human autoantigens.
authors.affiliation: Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Philipp
authors.forename: M
authors.initials: M
authors.lastname: Durazzo
authors.forename: C
authors.initials: C
authors.lastname: Trautwein
authors.forename: B
authors.initials: B
authors.lastname: Alex
authors.forename: P
authors.initials: P
authors.lastname: Straub
authors.forename: J G
authors.initials: JG
authors.lastname: Lamb
authors.forename: E F
authors.initials: EF
authors.lastname: Johnson
authors.forename: R H
authors.initials: RH
authors.lastname: Tukey
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
mesh_terms: D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology / Q000382:microbiology; D002908:Chronic Disease; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005455:Fluorescent Antibody Technique; D014453:Glucuronosyltransferase / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology; D003699:Hepatitis D / Q000276:immunology*; D006801:Humans; D007526:Isoelectric Point; D008969:Molecular Sequence Data
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; C060729:anti-liver kidney microsome antibody; D014453:Glucuronosyltransferase