Clinical Reviews in Allergy & Immunology

, Volume 18, Issue 2, pp 215–239 | Cite as

Xenobiotic-metabolizing enzymes as autoantigens in human autoimmune disorders

An update
Article

Conclusion

Several diseases are characterized by the presence of autoantibodies directed against either CYP or xenobiotic-metabolizing enzymes. They may be induced by toxic or idiopathic event. Very little is known about the mechanism of their triggering. When a toxic compound was identified, the metabolic part was quite well-characterized and variations of metabolism could be a risk factor in the development of the disease (e.g., dihydralazine-induced hepatitis). But in all the cases the abnormal immunological response is not understood, although it seems clear that the autoantibodies are not by themselves responsible for the disease.

Keywords

Clinical Review Autoimmune Hepatitis Immunology Volume Reactive Metabolite Tienilic Acid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6:1–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Beaune P, Pessayre D, Dansette PM, Mansuy M, Manns M Autoantibodies against cytochromes P450: role in human diseases. Adv Pharmacol 1994; 30:199–245.PubMedCrossRefGoogle Scholar
  3. 3.
    Poupon R, Homberg JC, Abuaf N, Petit J, Bodin F, Darnis F. Atteintes hépatiques dues à l'acide ténilique. Six observations avec présence d'anticorps antireticulum endoplasmique. Nouv Presse Med 1980; 9:1881–1884.PubMedGoogle Scholar
  4. 4.
    Zimmerman HJ, Lewis JH, Ishak KG, Maddrey W. Ticrynafen associated hepatic injury: analysis of 340 cases. Hepatology 1984; 4:315–323.PubMedCrossRefGoogle Scholar
  5. 5.
    Homberg JC, André C, Abuaf N. A new anti-liver-kidney-microsome antibody (anti-LKM2) in tienilic acid-induced hepatitis. Clin Exp Immunol 1984; 55:561–570.PubMedGoogle Scholar
  6. 6.
    Homberg JC, Abuaf N, Helmy-Khalil S, Biour M, Poupon R, Islam S, et al. Drug-induced hepatitis associated with anti-cytoplasmic organelle autoantibodies. Hepatology 1985; 5:722–727.PubMedCrossRefGoogle Scholar
  7. 7.
    Beaune P, Dansette PM, Mansuy D, Kiffel L, Finck M, Amar C, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sci USA 1987; 84:551–555.PubMedCrossRefGoogle Scholar
  8. 8.
    Lecoeur S, Andre C, Beaune PH. Tienilic acid-induced auto immune hepatitis: anti-LKM2 autoantibodies recognize a three-site conformational epitope on cytochrome P450 2C9. Mol Pharmacol 1996; 50:326–333.PubMedGoogle Scholar
  9. 9.
    Jean P, Pothier J, Dansette PM, Mansuy D, Viari A. Automated multiple analysis of protein structures: application to homologymodeling of cytochromes P450. Proteins 1997; 28:388–404.PubMedCrossRefGoogle Scholar
  10. 10.
    Dansette PM, Amar C, Valadon P, Pons C, Beaune PH, Mansuy D. Hydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes. Catalysis by a cytochrome P450IIC different from that responsible for mephenytoin hydroxylation. Biochem Pharmacol 1991; 41:553–560.PubMedCrossRefGoogle Scholar
  11. 11.
    Löpez-Garcia MP, Dansette PM, Valadon P, Amar C, Beaune PH, Guengerich FP, Mansuy D. Human liver P450s expressed in yeast as tools for rective metabolite formation studies: oxidative activation of tienilic acid by P450 2C9 and P450 2C10. Eur J Biochem 1993; 213:223–232.PubMedCrossRefGoogle Scholar
  12. 12.
    Mansuy D, Valadon P, Erdelmeier I, Löpez-Garcia MP, Amar C, Girault JP, Dansette PM. Thiophene-S-oxides as new reactive metabolites: formation by cytochrome P450-dependent oxidation and reaction with nucleophiles. J Am Chem Soc 1991; 113:7825, 7826.CrossRefGoogle Scholar
  13. 13.
    Pariente EA, Pessayre D, Bernuau J, Degott C, Benhamou JP. Dihydralazine hepatitis: report of a case and review of the literature. Digestion 1983; 27:47–52.PubMedGoogle Scholar
  14. 14.
    Roschlau G. Hepatitis mit konfluierenden Nekrosen durch Dihydralazin (Depressan). Zbl Allg Pathol Pathol Anat 1983;127:385–393.Google Scholar
  15. 15.
    Roschlau G. Virushepatitis gegen Arzneimittelhepatitis. Z Klin Med 1986; 41:817–819.Google Scholar
  16. 16.
    Reinhardt M, Machnik G, Krombholz B, Jahn G Die sogenannte Dihydralazin-Hepatitis. Ein Beitrag zur Pathogenese. Dtsch Z Verdau Stoffwechselkrankh 1985; 45:283–294.Google Scholar
  17. 17.
    Stricker BHC. Drug Induced Hepatic Injury. Amsterdam: Elsevier, 1992.Google Scholar
  18. 18.
    Bourdi M, Larrey D, Nataf J, Bernuau J, Pessayre D, Iwasaki M, et al. Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450 1A2: a specific marker of Dibydralazine-induced hepatitis. J Clin Invest 1990; 85:967–973.CrossRefGoogle Scholar
  19. 19.
    Bourdi M, Gautier JC, Mircheva J, Larrey D, Guillouzo A, Andre C, et al. Anti-liver microsomes, autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug. Mol Pharmacol 1992; 42:280–285.PubMedGoogle Scholar
  20. 20.
    Belloc C, Gauffre A, Andre C, Beaune PH. Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis. Pharmacogenetics 1997; 7:181–186.PubMedCrossRefGoogle Scholar
  21. 21.
    Bourdi M, Tinel M, Beaune PH, Pessayre D. Interactions of dihydralazine with cytochromes P4501A: a possible explanation for the appearance of anti-cytochrome P4501A2 autoantibodies. Mol Pharmacol 1994; 45:1287–1295.PubMedGoogle Scholar
  22. 22.
    Siegmund S, Franke G, Biebler KE, Donner I, Kallwellis R, Kairies M, et al. The influence of the acetylator phenotype for the clinical use of dihydralazine. Int J Clin Pharmaco Therapy Toxicol 1985; 23:S74-S78.Google Scholar
  23. 23.
    Trowell J, Peto R, Smith AC. Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium. Lancet 1975; 1(7911):821–824.PubMedCrossRefGoogle Scholar
  24. 24.
    Pohl LR, Pumford NR, Martin JL. Mechanisms, chemical structures and drug metabolism. Eur J Haematol 1996; (Suppl) 60: 98–104.Google Scholar
  25. 25.
    Kenna JG. Immunoallergic drug-induced hepatitis: lessons from halothane. J Hepatol 1997; 26:5–12.PubMedGoogle Scholar
  26. 26.
    Kharasch ED, Hankins D, Mautz D, and Thummel KE. Identification of the enzyme responsible for oxidative halothane metabolism implications for prevention of halothane hepatitis. Lancet 1996; 347:1367–1371.PubMedCrossRefGoogle Scholar
  27. 27.
    Eliasson, E, Gardner, I, Hume-Smith, H, de Waziers, I, Beaune, PH, Kenna, JG. Interindividual variability in P450 dependent generations of neoantigens in halothane hepatitis. Chem Biol Interact 1998; 116:123–141.PubMedCrossRefGoogle Scholar
  28. 28.
    Bourdi, M, Chen, W, Peter RM, Martin JL, Buters, JT, Nelson, SD, Pohl. LR. Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem Res Toxicol 1996; 9:1159–1166.PubMedCrossRefGoogle Scholar
  29. 29.
    Furst, SM, Luedke, D, Gaw, HH, Reich, R, Gandolfi AJ. Demonstration of a cellular immune reponse in halothane-exposed guinea pigs. Tox Appl Pharmacol 1997; 143:245–255.CrossRefGoogle Scholar
  30. 30.
    Leeder, JS, Riley, RJ, Cook, VA, Spielberg, SP. Human anti-cytochrome P450 antibodies in aromatic anticonvulsant-induced hypersensitivity reactions. J Pharmacol Exp Ther 1992; 263:360–367.PubMedGoogle Scholar
  31. 31.
    Lertratanangkoon K, Horning MG. Metabolism of carbamazepine. Drug Metab Dispos 1982; 10, 1–10.PubMedGoogle Scholar
  32. 32.
    Riley RJ, Roberts, P, Kitterhingham NR, Park BK. Formation of cytotoxic metabolites from phenytoin, imipramine, desipramine, amitriptyline and mianserin by mouse and human hepatic microsomes. Biochem Phamacol 1990; 39:1951–1958.CrossRefGoogle Scholar
  33. 33.
    Riley RJ, Maggs JL, Lambert C, Kitterhingham NR, Park BK. An in vitro study of the microsomal metabolism and cellular toxicity of phenytoin, sorbinil and mianserin. Br J Clin Pharmacol 1988; 26:577–588.PubMedGoogle Scholar
  34. 34.
    Wolkenstein, P, Tan C, Lecoeur S, Wechsler J, Garcia-Martin N, Charue D, et al. Covalent binding of carbamazepine reactive metabolites to P450 isoforms. Chem Biol Interact 1998; 113:39–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Leeder JS, Lu X, Timsit Y, Gaedigk A: Non-monooxygenase cytochromes P450 as potential human autoantigens in anticonvulsant hypersensitivity reactions. Pharmacogenetics 1998; 8:211–225.PubMedCrossRefGoogle Scholar
  36. 36.
    Pons C, Dansette PM, Gregeois, J, Homberg JC, Billett EE, Mansuy D. Human anti-mitochondria autoantibodies appearing in iproniazid induced immunoallergic hepatitis recognize human liver monoamine oxidase B. Biochem Biophys Res Commun 1996; 218:118–124.PubMedCrossRefGoogle Scholar
  37. 37.
    Shen S, Hargus, SJ, Martin BM, Pohl LR. Cytochrome P4502C11 is a target of diclofenac covalent binding in rats. Chem Res Toxicol 1997; 10:420–423.PubMedCrossRefGoogle Scholar
  38. 38.
    Pumford NR, Halmes NC, Johnson JA. Covalent binding of xenobiotics to specific proteins in the liver. Drug Metab Rev 1997; 29:39–58.PubMedGoogle Scholar
  39. 39.
    Cohen SD, Khairallah EA. Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug Metab Rev 1997; 29:59–78.PubMedGoogle Scholar
  40. 40.
    Spinner MW, Blizzard RM, Childs B. Clinical and genetic heterogeneity in idiopathic Addison's disease and hypoparathyroidism. J Clin Endocrinol Metab 1968; 28:795–804.PubMedCrossRefGoogle Scholar
  41. 41.
    Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990; 322:1829–1836.PubMedCrossRefGoogle Scholar
  42. 42.
    Betterle C, Greggio NA, Volpato M. Clinical review 93: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998; 83:1049–1055.PubMedCrossRefGoogle Scholar
  43. 43.
    Neufeld M, Maclaren NK, Blizzard RM. Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes. Med Baltimore 1981; 60:355–362.Google Scholar
  44. 44.
    Riley WJ. Autoimmune polyglandular syndromes. Horm Res 1992; 38:9–15.PubMedGoogle Scholar
  45. 45.
    Doniach D, Bottazzo GF. Polyendocrine Autoimmunity. Amsterdam: Elsevier North Holland, 1981, pp. 95–121.Google Scholar
  46. 46.
    McIntyre Gass JD. The syndrome of keratoconjunctivitis superficial moniliasis idiopathic hypoparathyroidism and Addison's disease. Am J Opthalmol 1962; 54:660–674.Google Scholar
  47. 47.
    Neufeld M, Blizzard RM. Polyglandular Autoimmune Disease. New York: Academic, 1980, pp. 357–365.Google Scholar
  48. 48.
    Aaltonen J, Bjorses P, Sandkuijl L, Perheentupa J, Peltonen L. An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nature Genet 1994; 8:83–87.PubMedCrossRefGoogle Scholar
  49. 49.
    Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nature Genet 1997; 17:393–398.PubMedCrossRefGoogle Scholar
  50. 50.
    Gibson TJ, Ramu C, Gemund C, Aasland R. The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. Trends Biochem Sci 1998; 23:242–244.PubMedCrossRefGoogle Scholar
  51. 51.
    Scott HS, Heino M, Peterson P, Mittaz L, Lalioti MD, Betterle C, et al. Common mutations in autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy patients of different origins. Molecular Endocrinol 1998; 12:1112–1119.CrossRefGoogle Scholar
  52. 52.
    Arulanantham K, Dwyer JM, Genel M. Evidence for defective immunoregulation in the syndrome of familial candidiasis endocrinopathy. N Engl J Med 1979; 300:164–168.PubMedCrossRefGoogle Scholar
  53. 53.
    Chilgren RA, Meuwissen HJ, Quie PG, Good RA, Hong R. The cellular immune defect in chronic mucocutaneous candidiasis. Lancet 1969; 1:1286–1288.PubMedCrossRefGoogle Scholar
  54. 54.
    Peterson P, Perheentupa J, Krohn KJ. Detection of candidal antigens in autoimmune polyglandular syndrome type I. Clin Diagn Lab Immunol 1996; 3:290–294.PubMedGoogle Scholar
  55. 55.
    Bednarek J, Furmaniak J, Wedlock N, Kiso Y, Baumann Antczak A, et al. Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison's disease. FEBS Lett 1992; 309:51–55.PubMedCrossRefGoogle Scholar
  56. 56.
    Krohn K, Uibo R, Aavik E, Peterson P, Savilahti K. Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alphahydroxylase. Lancet 1992; 339:770–773.PubMedCrossRefGoogle Scholar
  57. 57.
    Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison's disease. Lancet 1992; 339:1559–1562.PubMedCrossRefGoogle Scholar
  58. 58.
    Winqvist O, Gustafsson J, Rorsman F, Karlsson FA, Kampe O. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease. J Clin Invest 1993; 92:2377–2385.PubMedCrossRefGoogle Scholar
  59. 59.
    Winqvist O, Gebre Medhin G, Gustafsson J, Ritzen EM, Lundkvist O, Karlsson FA, Kampe O. Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure (see comments). J Clin Endocrinol Metab 1995; 80:1717–1723.PubMedCrossRefGoogle Scholar
  60. 60.
    Casey ML, MacDonald PC. Demonstration of steroid 17 alphahydroxylase activity in human fetal kidney, thymus, and spleen. Steroids 1982; 40:91–97.PubMedCrossRefGoogle Scholar
  61. 61.
    Nebert DW, Gonzalez FJ. P450 genes and evolutionary genetics. Hosp Pract Off Ed 1987; 22:63–74.PubMedGoogle Scholar
  62. 62.
    Song YH, Connor EL, Muir A, She JX, Zorovich B, Derovanesian D, Maclaren N. Autoantibody epitope mapping of the 21-hydroxylase antigen in autoimmune Addison's disease. J Clin Endocrinol Metab 1994; 78:1108–1112.PubMedCrossRefGoogle Scholar
  63. 63.
    Tanaka H, Asawa T, Powell M, Chen S, Smith BR, Furmaniak J. Autoantibody binding to steroid 21-hydroxylase: effect of five mutations. Autoimmunity 1997; 26:253–259.PubMedCrossRefGoogle Scholar
  64. 64.
    Hannigan NR, Jabs K, Perez Atayde AR, Rosen S. Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune syndrome. Pediatr Nephrol 1996; 10:511–514.PubMedCrossRefGoogle Scholar
  65. 65.
    Michele TM, Fleckenstein J, Sgrignoli AR, Thuluvath PJ. Chronic active hepatitis in the type I polyglandular autoimmune syndrome. Postgrad Med J 1994; 70:128–131.PubMedGoogle Scholar
  66. 66.
    Clemente MG, Obermayer Straub P, Meloni A, Strassburg CP, Arangino V., Tukey RH, et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1997; 82:1353–1361.PubMedCrossRefGoogle Scholar
  67. 67.
    Clemente MG, Meloni A, Obermayer Straub P, Frau F, Manns MP, De Virgiliis S. Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1. Gastroenterology 1998; 114:324–328.PubMedCrossRefGoogle Scholar
  68. 68.
    Manns MP, Griffin KJ, Sullivan KF, Johnson EF. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 1991; 88:1370–1378.PubMedCrossRefGoogle Scholar
  69. 69.
    Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, et al. Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 1994; 344:578–581.PubMedCrossRefGoogle Scholar
  70. 70.
    Manns MP, Zanger U, Gerken G, Sullivan KF, Meyer zum Buschenfelde KH, Meyer UA, Eichelbaum M. Patients with type II autoimmune hepatitis express functionally intact cytochrome P-450 dbl that is inhibited by LKM-1 autoantibodies in vitro but not in vivo. Hepatology 1990; 12:127–132.PubMedCrossRefGoogle Scholar
  71. 71.
    Sacher M, Blumel P, Thaler H, Manns M. Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies. J Hepatol 1990; 10:364–369.PubMedCrossRefGoogle Scholar
  72. 72.
    Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270: 414–423.PubMedGoogle Scholar
  73. 73.
    Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19:1513–1520.PubMedGoogle Scholar
  74. 74.
    Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18:998–1005.PubMedCrossRefGoogle Scholar
  75. 75.
    Homberg JC, Abuaf N, Bernard O, 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; 7:1333–1339.PubMedCrossRefGoogle Scholar
  76. 76.
    Manns MP, Griffin KJ, Quattrochi LC, Sacher M, Thaler H, Tukey RH, Johnson EF. Identification of cytochrome P450IA2 as a human autoantigen. Arch Biochem Biophys 1990; 280:229–232.PubMedCrossRefGoogle Scholar
  77. 77.
    Clifford BD, Donahue D, Smith L, Cable E, Luttig B, Manns M, Bonkovsky HL. High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C. Hepatology 1995; 21:613–619.PubMedGoogle Scholar
  78. 78.
    Ma Y, Peakman M, Lobo Yeo A, Wen L, Lenzi M, Gaken J, et al. Differences in immune recognition of cytochrome P45002D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clin Exp Immunol 1994; 97:94–99.PubMedCrossRefGoogle Scholar
  79. 79.
    Ma Y, Gregorio G, Gaken J, Muratori L, Bianchi LB, Mieli Vergani G, Vergani D. Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection. J Hepatol 1997; 26:1396–1402.PubMedCrossRefGoogle Scholar
  80. 80.
    Ruiz Moreno M, Rua MJ, Carreno V, Quiroga JA, Manns M, Meyer zum Buschenfelde KH. Autoimmune chronic hepatitis type 2 manifested during interferon therapy in children. J Hepatol 1991; 12:265, 266.PubMedCrossRefGoogle Scholar
  81. 81.
    Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and other disorders. Clin Exp Immunol 1973; 15:331–344.PubMedGoogle Scholar
  82. 82.
    Alvarez F, Bernard O, Homberg JC, Kreibich G. Anti-liver-kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum. J Exp Med 1985; 161:1231–1236.PubMedCrossRefGoogle Scholar
  83. 83.
    Kyriatsoulis A, Manns M, Gerken G, Lohse AW, Ballhausen W, Reske K, Meyer zum Buschenfelde KH. Distinction between natural and pathological autoantibodies by immunoblotting and densitometric subtraction: liver-kidney microsomal antibody (LKM) positive sera identify multiple antigens in human liver tissue. Clin Exp Immunol 1987; 70:53–60.PubMedGoogle Scholar
  84. 84.
    Codoner Franch P, Paradis K, Gueguen M, Bernard O, Costesec AA, Alvarez F. A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA). Clin Exp Immunol 1989; 75:354–358.PubMedGoogle Scholar
  85. 85.
    Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF. Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450dbl. J Clin Invest 1989; 83:1066–1072.PubMedCrossRefGoogle Scholar
  86. 86.
    Gueguen M, Yamamoto AM, Bernard O, Alvarez F. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 dbl. Biochem Biophys Res Commun 1989; 159:542–547.PubMedCrossRefGoogle Scholar
  87. 87.
    Kiffel L, Loeper J, Homberg JC, Leroux JP. A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis. Biochem Biophys Res Commun 1989; 159:283–289.PubMedCrossRefGoogle Scholar
  88. 88.
    Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA. Antibodies against human cytochrome P-450dbl in autoimmune hepatitis type II. Proc Natl Acad Sci USA 1988; 85:8256–8260.PubMedCrossRefGoogle Scholar
  89. 89.
    Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW, et al. Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 1988; 331:442–446.PubMedCrossRefGoogle Scholar
  90. 90.
    Yamamoto AM, Cresteil D, Boniface O, Clerc FF, Alvarez F. Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKM1). Eur J Immunol 1993; 23:1105–1111.PubMedCrossRefGoogle Scholar
  91. 91.
    Yamamoto AM, Mura C, De Lemos Chiarandini C, Krishnamoorthy R, Alvarez F. Cytochrome P450IID6 recognized by LKM1 antibody is not exposed on the surface of hepatocytes. Clin Exp Immunol 1993; 92:381–390.PubMedCrossRefGoogle Scholar
  92. 92.
    Duclos Vallee JC, Hajoui O, Yamamoto AM, Jacz Aigrain E, Alvarez F. Conformational epitopes on CYP2D6 are recognized by liver/kidney microsomal antibodies. Gastroenterology 1995; 108:470–476.PubMedCrossRefGoogle Scholar
  93. 93.
    De Lemos Chiarandini C, Alvarez F, Bernard O, Homberg JC, Kreibich G. Anti-liver-kidney microsome antibody is a marker for the rat hepatocyte endoplasmic reticulum. Hepatology 1987; 7:468–475.PubMedCrossRefGoogle Scholar
  94. 94.
    De Lemos Chiarandini C, Frey AB, Sabatini DD, Kreibich G. Determination of the membrane topology of the phenobarbital inducible rat liver cytochrome P-450 isoenzyme PB-4 using site-specific antibodies. J Cell Biol 1987; 104:209–219.PubMedCrossRefGoogle Scholar
  95. 95.
    Trautwein C, Ramadori G, Gerken G, Meyer zum Buschenfelde KH, Manns M. Regulation of cytochrome P450 IID by acute phase mediators in C3H/HeJ mice. Biochem Biophys Res Commun 1992; 182:617–623.PubMedCrossRefGoogle Scholar
  96. 96.
    Beaune PH, Lecoeur S, Bourdi M, Gauffre A, Belloc C, Dansette P, Mansuy D. Anti-cytochrome P450 autoantibodies in drug-induced disease. Eur J Haematol Suppl 1996; 60:89–92.Google Scholar
  97. 97.
    Eliasson E, Kenna JG. Cytochrome P450 2E1 is a cell surface auto antigen in halothane hepatitis. Mol Pharmacol 1996; 50:573–582.PubMedGoogle Scholar
  98. 98.
    Jarasch ED, Kartenbeck J, Bruder G, Fink A, Morre DJ, Franke WW. B-type cytochromes in plasma membranes isolated from rat liver, in comparison with those of endomembranes. J Cell Biol 1979; 80:37–52.PubMedCrossRefGoogle Scholar
  99. 99.
    Lenzi M, Bianchi FB, Cassani F, Pisi E. Liver cell surface expression of the antigen reacting with liver-kidney microsomal antibody (LKM). Clin Exp Immunol 1984; 55:36–40.PubMedGoogle Scholar
  100. 100.
    Loeper J, Descatoire V, Maurice M, Beaune P, Feldman G, Larrey D, Pessayre D. Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. Hepatology 1990; 11:850–858.PubMedCrossRefGoogle Scholar
  101. 101.
    Loeper J, Descatoire V, Maurice M, Beaune P, Belghiti J, Houssin D, et al. Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies. Gastroenterology 1993; 104:203–216.PubMedGoogle Scholar
  102. 102.
    Loeper J, Le Berre A, Pompon D. Topology inversion of CYP2D6 in the endoplasmic reticulum is not required for plasma membrane transport. Mol Pharmacol 1998; 53:408–414.PubMedGoogle Scholar
  103. 103.
    Loeper J, Louerat Oriou B, Duport C, Pompon D. Yeast expressed cytochrome P450 2D6 (CYP2D6) exposed on the external face of plasma membrane is functionally competent. Mol Pharmacol 1998; 54:8–13.PubMedGoogle Scholar
  104. 104.
    Robin MA, Maratrat M, Loeper J, Durand Schneider AM, Tinel M, Ballet F, et al. Cytochrome P4502B follows a vesicular route to the plasma membrane in cultured rat hepatocytes. Gastroenterology 1995; 108:1110–1123.PubMedCrossRefGoogle Scholar
  105. 105.
    Robin MA, Maratrat M, Le Roy M, Le Breton FP, Bonierbale E, Dansette P, et al. Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera. J Clin Invest 1996; 98:1471–1480.PubMedCrossRefGoogle Scholar
  106. 106.
    Stasiecki P, Oesch F, Bruder G, Jarasch ED, Franke WW. Distribution of enzymes involved in metabolism of polycyclic aromatic hydrocarbons among rat liver endomembranes and plasma membranes. Eur J Cell Biol 1980; 21:79–92.PubMedGoogle Scholar
  107. 107.
    Wu D, Cederbaum AI. Presence of functionally active cytochrome P450IIE1 in the plasma membrane of rat hepatocytes. Hepatology 1992; 15:515–524.PubMedCrossRefGoogle Scholar
  108. 108.
    Löhr H, Manns M, Kyriatsoulis A, Lohse AW Trautwein C, Meyer zum Buschenfelde KH, Fleischer B. Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis. Clin Exp Immunol 1991; 84:297–302.PubMedCrossRefGoogle Scholar
  109. 109.
    Crivelli O, Lavarini C, Chiaberge E, Amoroso A, Farci P, Negro F, Rizzetto M. Microsomal autoantibodies in chronic infection with the HBsAg associated delta (delta) agent. Clin Exp Immunol 1983; 54:232–238.PubMedGoogle Scholar
  110. 110.
    Burchell B, Nebert DW, Nelson DR, Bock KW, Iyanagi T, Jansen PL, et al. The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence. DNA Cell Biol 1991; 10:487–494.PubMedCrossRefGoogle Scholar
  111. 111.
    Dutton GJ. Glucoronidation of drugs and other compounds. Boca Raton, FL: CRC, 1980; p. 175.Google Scholar
  112. 112.
    Harding D, Jeremiah SJ, Povey S, Burchell B. Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1. Ann Hum Genet 1990; 54:17–21.PubMedCrossRefGoogle Scholar
  113. 113.
    Owens IS, Ritter JK. The novel bilirubin/phenol UDPglucuronosyltransferase UGT1 gene locus: implications for multiple nonhemolytic familial hyperbilirubinemia phenotypes. Pharmacogenetics 1992; 2:93–108.PubMedCrossRefGoogle Scholar
  114. 114.
    Straub P, Phillipp T, Lamb JC. Molecular characterization of a microsomal antigen in hepatitis D. 45th Annual Meeting of the American Association for the Study of Liver Diseases. Hepatology 1994; 20:427.Google Scholar
  115. 115.
    Strassburg CP, Obermayer Straub P, Alex B, Durazzo M, Rizzetto M, Tukey RH, Manns MP. Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology 1996; 111:1576–1586.PubMedCrossRefGoogle Scholar
  116. 116.
    Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology 1993; 105:1522–1528.PubMedGoogle Scholar
  117. 117.
    Johnson PJ, McFarlane IG, McFarlane BM, Williams R. Auto-immune features in patients with idiopathic chronic active hepatitis who are seronegative for conventional auto-antibodies. J Gastroenterol Hepatol 1990; 5:244–251.PubMedCrossRefGoogle Scholar
  118. 118.
    Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Buschenfelde KH. Characterisation of a new subgroup of auto immune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987; 1:292–294.PubMedCrossRefGoogle Scholar
  119. 119.
    MacFarlane JG, Williams R. Historical Overview. Heidelberg, Germany: Springer-Verlag, 1996, pp. 1–21.Google Scholar
  120. 120.
    Wächter B, Kyriatsoulis A, Lohse AW, Gerken G, Meyer zum Buschenfelde KH, Manns MP. Characterization of liver cytokeratin as a major target antigen of anti-SLA antibodies. J Hepatol 1990; 11:232–239.PubMedCrossRefGoogle Scholar
  121. 121.
    Wesierska-Gadek J, Grimm R, Hitchman E, Penner E. Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis. Gastroenterology 1998; 114:329–335.PubMedCrossRefGoogle Scholar
  122. 122.
    Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, et al. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 1981; 153:933–959.PubMedCrossRefGoogle Scholar
  123. 123.
    Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 1982; 31:11–24.PubMedCrossRefGoogle Scholar
  124. 124.
    Bass NM, Kirsch RE, Tuff SA, Marks I, Saunders SJ. Ligandin heterogeneity: evidence that the two non-identical subunits are the monomers of two distinct proteins. Biochim Biophys Acta 1977; 492:163–175.PubMedGoogle Scholar
  125. 125.
    Hayes JD. Purification and characterization of glutathione S-transferases P, S and N. Isolation from rat liver of Ybl Yn protein, the existence of which was predicted by subunit hybridization in vitro. Biochem J 1984; 224:839–852.PubMedGoogle Scholar
  126. 126.
    Hayes PC, Portmann B, Aldis PM, Williams R, Hayes JD. Glutathione S-Transferases and Carcinogenesis. London: Taylor and Francis, 1987, pp. 175–187.Google Scholar
  127. 127.
    Pickett CB, Telakowski Hopkins CA, Ding GJ, Argenbright L, Lu AY. Rat liver glutathione S-transferases. Complete nucleotide sequence of a glutathione S-transferase mRNA and the regulation of the Ya, Yb, and Yc mRNAs by 3-methylcholanthrene and phenobarbital. J Biol Chem 1984; 259:5182–5188.PubMedGoogle Scholar
  128. 128.
    Smith GJ, Ohl VS, Litwack G. Ligandin, the glutathione S-transferases, and chemically induced hepatocarcinogenesis: a review. Cancer Res 1977; 37:8–14.PubMedGoogle Scholar
  129. 129.
    Telakowski Hopkins CA, Rodkey JA, Bennett CD, Lu AY, Pickett CB. Rat liver glutathione S-transferases. Construction of a cDNA clone complementary to a Yc mRNA and prediction of the complete amino acid sequence of a Yc subunit. J Biol Chem 1985; 260:5820–5825.PubMedGoogle Scholar
  130. 130.
    Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 1995; 30:445–600.PubMedCrossRefGoogle Scholar
  131. 131.
    Mackay IR. The grey edges of autoimmune hepatitis. Int Hepatol Commun 1996; 5:191–200.CrossRefGoogle Scholar
  132. 132.
    Pessayre D. Toxic and Immune mechanisms leading to acute and subacute drug-induced liver injury. Paris: John Libbey Eurotext, 1993, pp. 23–39.Google Scholar
  133. 133.
    Guilbert B, Dighiero G, Avrameas S. Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization. J Immunol 1982; 128:2779–2787.PubMedGoogle Scholar
  134. 134.
    Parker DC. T cell-dependent B cell activation. Annu Rev Immunol 1993; 11: 331–360.PubMedGoogle Scholar
  135. 135.
    Cambier JC, Morrison DC, Chien MM, Lehmann KR. Modeling of T cell contact-dependent B cell activation. IL-4 and antigen receptor ligation primes quiescent B cells to mobilize calcium in response to Ia crosslinking. J Immunol 1991; 146:2075–2082.PubMedGoogle Scholar
  136. 136.
    Tinel M, Robin MA, Doostzadeh J, Maratrat M, Ballet F, Fardel N, et al. The interleukin-2 receptor down-regulates the expression of cytochrome P450 in cultured rat hepatocytes. Gastroenterology 1995; 109:1589–1599.PubMedCrossRefGoogle Scholar
  137. 137.
    Druet P, Sheela R, Pelletier I. Th1 and Th2 cells in autoimmunity. Clin Exp Immunol. 1995; 101 Suppl 1:9–12.PubMedGoogle Scholar
  138. 138.
    Pelletier L, Pasquier R, Rossert J, Druet P. HgCl2 induces nonspecific immunosuppression in Lewis rats. Eur J Immunol 1987; 17:49–54.PubMedCrossRefGoogle Scholar
  139. 139.
    Pelletier L, Rossert J, Pasquier R, Vial MC, Druet P. Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat. Scand J Immunol 1990; 31:65–74.PubMedCrossRefGoogle Scholar
  140. 140.
    Fowell D, McKnight AJ, Powrie F, Dyke R, Mason D. Subsets of CD4+ T cells and their roles in the induction and prevention of autoimmunity. Immunol Rev 1990; 123:37–64.CrossRefGoogle Scholar
  141. 141.
    Goldman M, Druet P, Gleichmann E. TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemicallyinduced autoimmunity. Immunol Today 1991; 12:223–227.PubMedCrossRefGoogle Scholar
  142. 142.
    MacKnight AJ, Barclay AN, Mason DW. Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells. Eur J Immunol 1991; 21:1187–1194.CrossRefGoogle Scholar
  143. 143.
    Davies JM. Molecular mimicry: can epitope mimicry induce autoimmune disease? Immunol Cell Biol 1997; 75:113–126.PubMedCrossRefGoogle Scholar
  144. 144.
    Oldstone MB. Molecular mimicry and autoimmune disease. Cell 1987; 50:819–820.PubMedCrossRefGoogle Scholar
  145. 145.
    Lenzi M, Johnson PJ, McFarlane IG, Ballardini G, Smith HM, McFarlane BM, et al. Antibodies to hepatitis C virus in autoimmune liver disease: evidence for geographical heterogeneity. Lancet 1991; 338:277–280.PubMedCrossRefGoogle Scholar
  146. 146.
    Michitaka K, Durazzo M, Tillmann, Walker D, Philipp T, Manns MP. Analysis of hepatitis C virus genome in patients with autoimmune hepatitis type 2. Gastroenterology 1994; 106:1603–1610.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  1. 1.INSERM U 490, Toxicologie moléeculaireUniversité René DescartesParis Cedex 06France

Personalised recommendations