Increased incidence of anti-LKM autoantibodies in a consecutive cohort of hepatitis C patients from central Greece
AuthorDalekos, G. N.; Makri, E.; Loges, S.; Obermayer-Straub, P.; Zachou, K.; Tsikrikas, T.; Schmidt, E.; Papadamou, G.; Manns, M. P.
Objectives In Greece, there are insufficient data regarding the presence of non-organ and liver-related autoantibodies in hepatitis C patients. This study in a consecutive cohort of 39 such patients from central Greece investigates (1) the prevalence of non-organ and liver-related autoantibodies, and (2) the reactivity of anti-liver-kidney microsomal type 1 antibodies (in the case of positivity with at least one of the methods used) against their molecularly defined antigens. Design All serum samples were tested by standard and molecular assays for the presence of anti-nuclear antibodies, smooth muscle antibodies, anti-liver-kidney microsomal type 1 antibodies, antibodies against parietal cells, anti-CYP2A6, anti-CYP1A2 and anti-CYP2D6 autoantibodies. Methods Indirect immunofluorescence, competitive enzyme-linked immunosorbent assays, immunoblotting and novel radioligand assays based on immunoprecipitation of [S-35]-methionine labelled recombinant CYP2A6, CYP1A2 and CYP2D6 His-taq fusion proteins produced by in vitro transcription/translation were used. Results Seven out of 39 patients (17.9%) tested positive for smooth muscle antibodies, 2/39 (5.1%) tested positive for anti-nuclear antibodies, 1/39 (2.5%) tested positive for parietal cell antibodies, and 4/39 (10.3%) were found to be anti-liver-kidney microsomal positive (with at least one of the methods used). All sera were negative for anti-CYP2A6 and anti-CYP1A2 autoantibodies. Three out of four anti-liver-kidney microsomal positive samples had the typical liver-kidney microsomal staining pattern shown by indirect immunofluorescence. However, none tested positive for anti-CYP2D6 autoantibodies using the competitive CYP2D6 enzyme-linked immunosorbent assay, the specific CYP2D6 radioligand assay, and western blot using either human microsomes or recombinant CYP2D6. The fourth patient tested negative for anti-liver-kidney autoantibodies by either indirect immunofluorescence or the competitive enzyme-linked immunosorbent assay, but was repeatedly positive for anti-CYP2D6 autoantibodies by the sensitive and specific radioligand assay. Western blot experiments using human microsomes in this patient serum revealed two bands of 50 kDa and 55 kDa that documented as anti-CYP2D6 and anti-uridine triphosphate glucuronosyltransferase autoantibodies when recombinant CYP2D6 and recombinant uridine triphosphate glucuronosyltransferase autoantigens were used for immunoblot, respectively. Conclusions A relatively high incidence of anti-liver-kidney microsomal autoantibodies (10.3%) was found in a consecutive sample of Greek patients with hepatitis C. The expanded panel of assays, however, failed to document CYP2D6 as the target autoantigen of anti-liver-kidney microsomal autoantibodies in most patients. We report for the first time the detection of parietal cell antibodies and both anti-CYP2D6 (anti-liver-kidney microsomal type 1) and anti-uridine triphosphate glucuronosyltransferase (anti-liver-kidney microsomal type 3) autoantibodies in patients who were hepatitis C positive/hepatitis D negative. Further studies are needed to confirm our findings and to determine whether these preliminary results have a clinical importance or not. Eur J Gastroenterol Hepatol 14:35-42 (C) 2002 Lippincott Williams Wilkins.
Showing items related by title, author, creator and subject.
Autoantibodies and autoantigens associated with autoimmune hepatitis and viruses-induced autoimmune response: Significant tools in clinical practice and in the study of pathogenesis of autoimmune hepatic diseases Dalekos, G. N. (2004)Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergamma-globulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive ...
Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics Gatselis, N. K.; Zachou, K.; Koukoulis, G. K.; Dalekos, G. N. (2015)Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic ...
Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus-infected patients is associated with the possession of HLA B51 Bogdanos, D. P.; Lenzi, M.; Okamoto, M.; Rigopoulou, E. I.; Muratori, P.; Ma, Y.; Muratori, L.; Tsantoulas, D.; Mieli-Vergani, G.; Bianchi, F. B.; Vergani, D. (2004)Liver Kidney Microsomal autoantibody type 1(LKM1) directed to cytochrome P4502D6 (CYP2D6) characterises autoimmune hepatitis type-2 (AIH-2), but is also found in a proportion of chronic hepatitis C virus (HCV) infected ...