Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis

Approximately 13% of patients with chronic hepatitis D virus (HDV) infection have liver-kidney microsomal antibodies type 3 (LKM-3) directed against family 1 uridine 5'-diphosphate-glucuronosyl-transferases (UGT-1). The aim of this study was to characterize the prevalence and specificity of LKM-3 by recombinant antigen testing systems.

Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed using baculovirus-generated human UGT-1.1 and -1.6 and rabbit UGT-1.6. Sera from patients with HDV (n = 50), autoimmune hepatitis (AIH) type 2 (n = 50), hepatitis B virus (n = 26), hepatitis C virus (HCV) (n = 25), and LKM-1 autoantibody-positive HCV (n = 14) and sera from normal controls (n = 50) and italian patients with HDV and known LKM-3 autoantibodies were studied.

Six percent of patients with HDV from Germany and 8% of patients with type 2 AIH had LKM-3. Sera from italian patients with HDV and patients with AIH type 2 recognized all three recombinant UGT-1. HDV sera from Germany selectively recognized human UGT-1. LKM-3 titers were lower in HDV than in AIH. One patient with AIH had LKM-3 as the only marker of AIH.

This study indicates a molecular target and titer difference of LKM-3 autoantibodies in German subjects with HDV and AIH. It also suggests a geographic target and titer difference of LKM-3 in HDV. LKM-3 are identified as a rare and previously undescribed independent marker of AIH.