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Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis

1996; Elsevier BV; Volume: 111; Issue: 6 Linguagem: Inglês

10.1016/s0016-5085(96)70020-3

1528-0012

CP Straßburg, Petra Obermayer–Straub, B. Alex, Marilena Durazzo, M. Rizzetto, R H Tukey, MP Manns,

Liver Diseases and Immunity

Background & Aims: Approximately 13% of patients mediated syndromes remains striking.Different markers with chronic hepatitis D virus (HDV) infection have liverof autoimmunity and clinically apparent immune-medikidney microsomal antibodies type 3 (LKM-3) directed ated syndromes are present in 5%-70% of patients. [2][4] against family 1 uridine 5-diphosphate-glucuronosyl-These markers include the rheumatoid factor and antitransferases (UGT-1).The aim of this study was to chartissue antibodies such as antithyroid, antinuclear, acterize the prevalence and specificity of LKM-3 by anti-smooth muscle, and anti-liver-kidney microsomal recombinant antigen testing systems.Methods: Enzyme-(LKM) antibodies.Clinical syndromes such as salivary linked immunosorbent assay (ELISA) and Western blot gland lesions, cryoglobulinemia, lichen planus, and were performed using baculovirus-generated human membranoproliferative glomerulonephritis also occur.In UGT-1.1 and -1.6 and rabbit UGT-1.6.Sera from pacontrast, infection with the hepatitis B virus (HBV) is tients with HDV (n Å 50), autoimmune hepatitis (AIH) not associated with a high prevalence of autoimmunity, type 2 (n Å 50), hepatitis B virus (n Å 26), hepatitis C whereas a similar association exists in patients infected virus (HCV) (n Å 25), and LKM-1 autoantibody-positive HCV (n Å 14) and sera from normal controls (n Å 50) with the hepatitis D virus (HDV). 5and Italian patients with HDV and known LKM-3 autoan-Crivelli et al., using indirect immunofluorescence tibodies were studied.Results: Six percent of patients(IIF), were the first to describe autoantibodies against with HDV from Germany and 8% of patients with type microsomal antigens in 13% of Italian patients with 2 AIH had LKM-3.Sera from Italian patients with HDV chronic HDV infection. 6 Because the IIF pattern differed and patients with AIH type 2 recognized all three recomfrom the previously described LKM-1 7 and LKM-2 8 aubinant UGT-1.HDV sera from Germany selectively rectoantibodies, these autoantibodies were termed LKM-3.ognized human UGT-1.LKM-3 titers were lower in HDV LKM-1 autoantibodies are the hallmark of autoimmune than in AIH.One patient with AIH had LKM-3 as the hepatitis (AIH) type 2 and have been found to be mainly only marker of AIH.Conclusions: This study indicates directed against linear and conformational epitopes of a molecular target and titer difference of LKM-3 autoancytochrome P450 2D6. 9-13They also occur in 2%-5% tibodies in German subjects with HDV and AIH.It also of patients with chronic HCV infection in whom they suggests a geographic target and titer difference of LKM-3 in HDV.LKM-3 are identified as a rare and preappear to recognize heterogenous targets. [13][4][15] LKM-2 viously undescribed independent marker of AIH.autoantibodies occur in tienilic acid-induced hepatitis and are directed against cytochrome P450 2C9. 8 Only recently, the molecular target of LKM-3 autoantibodies Abbreviations used in this study: AIH, autoimmune hepatitis;1989, 1 it has been implicated as the cause of chronic ELISA, enzyme-linked immunosorbent assay; LKM, liver-kidney microsomal antibodies; IIF, indirect immunofluorescence; PCR, polymer-viral hepatitis as well as an inductor and potential cause ase chain reaction; UGT, uridine 5-diphosphate-glucuronosyltransof autoimmunity. 2Although its etiopathogenic role in ferase; OD, optical density.autoimmunity is incompletely understood, the variety of