{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:47:03Z","timestamp":1790930823415,"version":"4.1.0"},"reference-count":29,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:p>Liver\/kidney microsomal antibody type 1 (LKM-1), the serological marker of a subset of autoimmune hepatitis, is also present in a proportion of patients with hepatitis C virus (HCV) related chronic liver disease. To characterise further this autoreactivity and to evaluate whether an autoantibody giving an identical immunofluorescence staining, and detected in two different clinical conditions, involves the same antigenic target(s), sera from autoimmune and HCV infected patients were tested with native, recombinant, and synthetic antigens. Sixty five sera were selected on the basis of the typical immunofluorescence pattern: 50 patients had serological markers of HCV infection, the remaining 15 suffered from autoimmune hepatitis. The reactivity of each serum with rat and human microsomal fractions, full length human recombinant CYP2D6, and two synthetic peptides spanning the amino acid regions 257-269 and 373-398 of CYP2D6 was systematically investigated by immunoblotting. Fourteen (93%) sera from autoimmune hepatitis patients and 39 (78%) from HCV infected patients reacted with rat and\/or human microsomal polypeptides of 39 kD, 50 kD, 58 kD, and 66 kD in different associations, the 50 kD band being the most frequently observed. Reactivity to CYP2D6 and its amino acid sequence 257-269 was significantly more common in autoimmune hepatitis than in HCV infected patients (p &lt; 0.001 and p &lt; 0.0003, respectively). LKM-1 reactivity is directed against heterogeneous and not entirely defined autoantigens. The main target in autoimmune sera is CYP2D6 and its 257-269 amino acid region, while sera from patients with HCV infection are more likely to recognise other microsomal targets, the molecular identity of which is currently unknown.<\/jats:p>","DOI":"10.1136\/gut.37.3.406","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"406-412","source":"Crossref","is-referenced-by-count":70,"title":["Heterogeneity of liver\/kidney microsomal antibody type 1 in autoimmune hepatitis and hepatitis C virus related liver disease."],"prefix":"10.1136","volume":"37","author":[{"given":"L","family":"Muratori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Lenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Cataleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Mieli-Vergani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Vergani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F B","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1995,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.1840070626","article-title":"Chronic active hepatitis associated with antiliver\/kidney microsome antibody type 1: a second type of 'autoimmune' hepatitis","volume":"7","author":"true","year":"1987","unstructured":"Homberg JC, Abuaf N, Bernard 0, Islam S, Alvarez F, Khalil SH, et al. Chronic active hepatitis associated with antiliver\/kidney microsome antibody type 1: a second type of 'autoimmune' hepatitis. Hepatology 1987; 7: 1333-9.","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/0140-6736(90)90070-L","article-title":"Type 2 autoimmune hepatitis and hepatitis C virus infection","volume":"335","author":"Lenzi, M.; Ballardini, G.; Fusconi, M.; Cassani, F.; Selleri, L.; Volta, U.","year":"1990","unstructured":"Lenzi M, Ballardini G, Fusconi M, Cassani F, Selleri L, Volta U, et al. Type 2 autoimmune hepatitis and hepatitis C virus infection. Lancet 1990; 335: 258-9.","journal-title":"Lancet"},{"key":"ref_3","first-page":"223","article-title":"Hepatitis C viraemia in adults with type 2 autoimmune hepatitis","volume":"34","author":"Garson, J.A.; Lenzi, M.; Ring, C.; Cassani, F.; Ballardini, G.; Briggs, M.","year":"1991","unstructured":"Garson JA, Lenzi M, Ring C, Cassani F, Ballardini G, Briggs M, et al. Hepatitis C viraemia in adults with type 2 autoimmune hepatitis. J7 Med Virol 1991; 34: 223-6."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/hep.1840160304","article-title":"Liver\/kidney microsome antibody type 1 and hepatitis C virus infection","volume":"16","author":"Lunel, F.; Abuaf, N.; Franguel, L.; Grippon, P.; Perrin, M.; Le Coz, Y.","year":"1992","unstructured":"Lunel F, Abuaf N, Franguel L, Grippon P, Perrin M, Le Coz Y, et al. Liver\/kidney microsome antibody type 1 and hepatitis C virus infection. Hepatology 1992; 16: 630-6.","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/0140-6736(90)93297-3","article-title":"Anti-HCV testing in autoimmune hepatitis and primary biliary cirrhosis","volume":"336","author":"Fusconi, M.; Lenzi, M.; Ballardini, G.; Miniero, R.; Cassani, F.; Zauli, D.","year":"1990","unstructured":"Fusconi M, Lenzi M, Ballardini G, Miniero R, Cassani F, Zauli D, et al. Anti-HCV testing in autoimmune hepatitis and primary biliary cirrhosis. Lancet 1990; 336: 823.","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1084\/jem.161.5.1231","article-title":"Anti-liverkidney microsome antibody recognizes a 50 000 molecular weight protein of the endoplasmic reticulum","volume":"161","year":"1985","unstructured":"Alvarez F, Bernard 0, Homberg JC, Kreibich G. Anti-liverkidney microsome antibody recognizes a 50 000 molecular weight protein of the endoplasmic reticulum. J Exp Med 1985; 161: 1231-6.","journal-title":"J Exp Med"},{"key":"ref_7","first-page":"1326","article-title":"Antibodies to liver\/kidney microsome, in chronic active hepatitis recognize specific forms of","volume-title":"hepatic cytochrome P-450. Gastroenterology 1988; 95","unstructured":"Waxman DJ, Lapenson DP, Krishnan M, Bernard 0, Kreibich G, Alvarez F. Antibodies to liver\/kidney microsome, in chronic active hepatitis recognize specific forms of hepatic cytochrome P-450. Gastroenterology 1988; 95: 1326-31."},{"key":"ref_8","first-page":"8256","article-title":"Antibodies against human cytochrome P450-dbl in autoimmune","volume-title":"hepatitis type II. Proc Natl Acad Sci","volume":"85","author":"Zanger, U.M.; Hauri, H.P.; Loeper, J.; Homberg, J.C.; Meyer, U.A.","year":"1988","unstructured":"Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA. Antibodies against human cytochrome P450-dbl in autoimmune hepatitis type II. Proc Natl Acad Sci USA 1988; 85: 8256-60."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1084\/jem.168.2.801","article-title":"Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily","volume":"168","year":"1988","unstructured":"Gueguen M, Meunier-Rotival M, Bernard 0, Alvarez F. Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily. J Exp Med 1988; 168: 801-6.","journal-title":"J Exp Med"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1172\/JCI113949","article-title":"Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db l","volume":"83","author":"Manns, M.P.; Johnson, E.F.; Griffin, K.J.; Tan, E.M.; Sullivan, K.F.","year":"1989","unstructured":"Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF. Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db l. J Clin Invest 1989; 83: 1066-72.","journal-title":"J Clin Invest"},{"key":"ref_11","first-page":"354","article-title":"A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA). Clin Exp Immunol","volume":"75","year":"1989","unstructured":"Codoner Franch P, Paradis K, Gueguen M, Bernard 0, Costesec AA, Alvarez F. A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA). Clin Exp Immunol 1989; 75: 354-8."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1172\/JCI115443","article-title":"LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase","volume":"88","author":"Manns, M.P.; Griffin, K.J.; Sullivan, K.F.; Johnson, E.F.","year":"1991","unstructured":"Manns MP, Griffin KJ, Sullivan KF, Johnson EF. 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Glin Exp Immunol 1993; 92: 373-80.","journal-title":"Glin Exp Immunol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0140-6736(93)92541-Z","article-title":"Case against subclassification of type II autoimmune chronic active hepatitis","volume":"341","author":"Ma, Y.; Peakman, M.; Lenzi, M.; Thomas, M.G.; Farzeneh, F.; Ballardini, G.; et at","year":"1993","unstructured":"Ma Y, Peakman M, Lenzi M, Thomas MG, Farzeneh F, Ballardini G, et at. Case against subclassification of type II autoimmune chronic active hepatitis. Lancet 1993; 341: 60.","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1016\/0016-5085(93)90657-X","article-title":"Characterization of anti-liver\/kidney microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera","volume":"104","author":"Yamamoto, A.M.; Cresteil, D.; Homberg, J.C.; Alvarez, F.","year":"1993","unstructured":"Yamamoto AM, Cresteil D, Homberg JC, Alvarez F. Characterization of anti-liver\/kidney microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera. GastroenterologAy 1993; 104: 1762-7.","journal-title":"GastroenterologAy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/eji.1830230519","article-title":"Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKMI)","volume":"23","year":"1993","unstructured":"Yamamoto AM, Cresteil D, Boniface 0, Clerc FF, Alvarez F. Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKMI). Eur J Immunol 1993; 23: 1105-11.","journal-title":"Eur J Immunol"},{"key":"ref_17","first-page":"331","article-title":"Microsomal antibodies in active chronic hepatitis and other disorders. Clin Exp Immunol","volume":"15","author":"Rizzetto, M.; Swana, G.; Doniach, D.","year":"1973","unstructured":"Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and other disorders. Clin Exp Immunol 1973; 15: 331-4."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hep.1840180435","article-title":"Meeting report: international autoimmune hepatitis group","volume":"18","author":"Johnson, P.J.; McFarlane, I.G.","year":"1993","unstructured":"Johnson PJ, McFarlane IG. Meeting report: international autoimmune hepatitis group. Hepatology 1993; 18: 998-1005.","journal-title":"Hepatology"},{"key":"ref_19","first-page":"253","article-title":"Counterimmunoelectrophoreis (CIE) for the detection of anti-liver-kidney microsome (LKM) antibodies in the sera of patients with chronic liver disease","volume":"111","author":"Lenzi, M.; Fusconi, M.; Selleri, L.; Caselli, A.; Cassani, F.; Bianchi, F.B.","year":"1988","unstructured":"Lenzi M, Fusconi M, Selleri L, Caselli A, Cassani F, Bianchi FB, et al. Counterimmunoelectrophoreis (CIE) for the detection of anti-liver-kidney microsome (LKM) antibodies in the sera of patients with chronic liver disease. JImmunolMethods 1988; 111: 253-9.","journal-title":"JImmunolMethods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"277","author":"Laemli, U.","year":"1970","unstructured":"Laemli U. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 277: 680-5.","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","article-title":"Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications","volume":"76","author":"Towbin, H.; Staehlin, T.; Gordon, J.","year":"1979","unstructured":"Towbin H, Staehlin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_22","first-page":"568","article-title":"Absent, decreased, or variant P450dbl in livers with poor capacity for debrisoquine metabolism","volume-title":"P450: Biochemistry and biophysics","author":"Zanger, U.M.; Meyer, U.A.","year":"1989","unstructured":"Zanger UM, Meyer UA. Absent, decreased, or variant P450dbl in livers with poor capacity for debrisoquine metabolism. In: Schuster I, ed. Cytochrome P450: Biochemistry and biophysics. London: Taylor & Francis, 1989: 568-71."},{"key":"ref_23","first-page":"94","article-title":"Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clin Exp Immunol","volume":"97","author":"Ma, Y.; Peakman, M.; Lobo-Yeo, A.; Wen, L.; Lenzi, M.; Gaken, J.","year":"1994","unstructured":"Ma Y, Peakman M, Lobo-Yeo A, Wen L, Lenzi M, Gaken J, et al. Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clin Exp Immunol 1994; 97: 94-9."},{"key":"ref_24","first-page":"1466","article-title":"Enhanced detection by PCR of hepatitis C virus RNA","volume":"338","author":"Garson, J.A.; Ring, C.; Tuke, P.W.; Tedder, R.S.","year":"1991","unstructured":"Garson JA, Ring C, Tuke PW, Tedder RS. Enhanced detection by PCR of hepatitis C virus RNA. Lancet 1991; 338: 1466-7.","journal-title":"Lancet"},{"key":"ref_25","first-page":"124","article-title":"Testing for hepatitis C virus sequences in peripheral blood mononuclear cells of patients with chronic hepatitis C in the absence of serum hepatitis C virus RNA","volume":"14","author":"Muratori, L.; Giostra, F.; Cataleta, M.; Francesconi, R.; Ballardini, G.; Cassani, F.","year":"1994","unstructured":"Muratori L, Giostra F, Cataleta M, Francesconi R, Ballardini G, Cassani F, et al. Testing for hepatitis C virus sequences in peripheral blood mononuclear cells of patients with chronic hepatitis C in the absence of serum hepatitis C virus RNA. Liver 1994; 14: 124-8.","journal-title":"Liver"},{"key":"ref_26","first-page":"367","article-title":"Type II autoimmune hepatitis: the conundrum of cytochrome P4501ID6. Clin Exp Immunol","volume":"92","author":"Vergani, D.; Mieli-Vergani, G.","year":"1993","unstructured":"Vergani D, Mieli-Vergani G. Type II autoimmune hepatitis: the conundrum of cytochrome P4501ID6. Clin Exp Immunol 1993; 92: 367-8."},{"key":"ref_27","first-page":"1870","article-title":"Type II autoimmune hepatitis. What is the role of the","volume-title":"hepatitis C virus? Gastroenterology 1993; 104","author":"Vergani, D.; Mieli-Vergani, G.","unstructured":"Vergani D, Mieli-Vergani G. Type II autoimmune hepatitis. What is the role of the hepatitis C virus? Gastroenterology 1993; 104: 1870-3."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1056\/NEJM199207303270502","article-title":"A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus","volume":"327","author":"Karjalainen, J.; Martin, J.M.; Knip, M.; Ilonen, J.; Robinson, B.H.; Savilahti, E.","year":"1992","unstructured":"Karjalainen J, Martin JM, Knip M, Ilonen J, Robinson BH, Savilahti E, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 1992; 327: 302-7.","journal-title":"N Engl J Med"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1016\/0016-5085(94)90426-X","article-title":"Primary and secondary liver-kidney microsomal autoantibody response following infection with hepatitis C virus","volume":"106","author":"Mackie, F.D.; Peakman, M.; Ma, Y.; Sallie, R.; Smith, H.; Davies, E.T.","year":"1994","unstructured":"Mackie FD, Peakman M, Ma Y, Sallie R, Smith H, Davies ET, et al. Primary and secondary liver-kidney microsomal autoantibody response following infection with hepatitis C virus. 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