Elsevier

The Lancet

Volume 344, Issue 8922, 27 August 1994, Pages 578-581
The Lancet

Articles
Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D

https://doi.org/10.1016/S0140-6736(94)91966-6Get rights and content

Abstract

Summary

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 molecularweight 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.

References (33)

  • L. Sutherland et al.

    Characterization of a human bilirubin UDP-glucuronosyltransferase stably expressed in hamster lung fibroblast cell cultures

    FEBS Lett

    (1992)
  • Pj Bosma et al.

    A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II

    Gastroenterology

    (1993)
  • M. Manns et al.

    Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450 dbl

    J Clin Invest

    (1989)
  • Um Zanger et al.

    Antibodies against human cytochrome P-450 dbl in autoimmune hepatitis type II

    Proc Natl Acad Sci USA

    (1988)
  • Mp Manns et al.

    LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase

    J Clin Invest

    (1991)
  • Mj Amengual et al.

    Autoantibodies in chronic delta virus infection recognize a common protein of 46 kD in rat forestomach basal cell layer and stellate thymic epithelial cells

    Clin Exp Immunol

    (1989)
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