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Prevalence and Significance of Autoantibodies in Acute and Chronic Liver Diseases and Hepatocellular Carcinoma

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Liver Immunology

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Abstract

Generally speaking, autoantibodies are B cell generated and also serologically detectable evidence of a loss of tolerance against cellular self structures, which can originate from different subcellular compartments (1–3). Autoantibodies have been described that target membrane-bound proteins of the cell and nuclear membranes and that reside in the cytoplasm or in other organelles such as the endoplasmic reticulum (Table 1) or mitochondria (Table 2). The proteins that are targeted include structural components such as actin or myosin and functional proteins such as metabolizing enzymes including cytochrome P450 (CYP), UDP-glucuronosyltransferases (UGTs), or pyruvate dehydrogenase (PDH). The identification of a specific epitope has stimulated research in an effort to characterize autoantibody-autoantigen reactivity as a tool to gain insight into the mechanisms of and the players involved in autoimmunity. However, the demonstration of a specific autoepitope reactivity does not preclude the possibility of crossreactivity of an exogenous antigen recognized by the immune system that displays homology with endogenous proteins of the body.

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References

  1. Strassburg CP, Obermayer-Straub P, Manns MP Autoimmunity in hepatitis C and D virus infection. J Viral Hepatol 1996; 3:49–59.

    Article  CAS  Google Scholar 

  2. Strassburg CP, Jaeckel E, Manns MR Anti-mitochondrial antibodies and other immunological tests in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999; 11:595–601.

    Article  PubMed  CAS  Google Scholar 

  3. Strassburg CP, Manns MP. Autoantibodies and autoantigens in autoimmune hepatitis. Semin Liver Dis 2002; 22:339–352.

    Article  PubMed  CAS  Google Scholar 

  4. Tan MT. Autoantibodies in pathology and cell biology. Cell 1991; 67:841–842.

    Article  PubMed  CAS  Google Scholar 

  5. Strassburg CP, Manns MP. Autoimmune tests in primary biliary cirrhosis. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 585–599.

    Article  PubMed  CAS  Google Scholar 

  6. Tan EM, Chan EKL, Sullivan KF, Rubin RL. Antinuclear antibodies (ANAs): diagnostically specific immune markers and clues toward the understanding of systemic autoimmunity. Clin Immunol Immunopathol 1988; 47:121–141.

    Article  PubMed  CAS  Google Scholar 

  7. Strassburg CP, Manns MP. Antinuclear antibody (ANA) patterns in hepatic and extrahepatic autoimmune disease. J Hepatol 1999; 31:751.

    Article  PubMed  CAS  Google Scholar 

  8. Strassburg CP, Alex B, Zindy F, et al. Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases. J Hepatol 1996; 25:859–866.

    Article  PubMed  CAS  Google Scholar 

  9. Dighiero G, Lymberi P, Monot C, Abuaf N. Sera with high levels of anti-smooth muscle and anti-mitochondrial antibodies frequently bind to cytoskeleton proteins. Clin Exp Immunol 1990; 82:52–56.

    Article  PubMed  CAS  Google Scholar 

  10. Kurki P, Miettinen A, Linder E, Pikkarainen P, Vuoristo M, Salaspuro MP. Different types of smooth muscle antibodies in chronic active hepatitis and primary biliary cirrhosis: their diagnostic and prognostic significance. Gut 1980; 21:878–884.

    Article  PubMed  CAS  Google Scholar 

  11. Lidman K, Biberfeld G, Fagraeus A, et al. Anti-actin specificity of human smooth muscle antibodies in chronic active hepatitis. Clin Exp Immunol 1976; 24:266–272.

    PubMed  CAS  Google Scholar 

  12. Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Buschenfelde KH. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987; 1:292–294.

    Article  PubMed  CAS  Google Scholar 

  13. Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology 1993; 18:1–9.

    PubMed  CAS  Google Scholar 

  14. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis [see comments]. Lancet 2000; 355:1510–1515.

    Article  PubMed  CAS  Google Scholar 

  15. Gelpi C SE, Rodriguez-Sanchez JL Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion. Proc Natl Acad Sci USA 1992; 89:9739–9743.

    Article  PubMed  CAS  Google Scholar 

  16. Tukey RH, Strassburg CP, Mackenzie PI. Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol 2002; 62:446–450.

    Article  PubMed  CAS  Google Scholar 

  17. Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and other disorders. Clin Exp Immunol 1973; 15:331–344.

    PubMed  CAS  Google Scholar 

  18. Homberg JC, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with anti liver/kidney microsome type 1: a second type of “autoimmune” hepatitis. Hepatology 1987; 7:1333–1359.

    Article  PubMed  CAS  Google Scholar 

  19. Guenguen M, Meunier-Rotival M, Bernard O, Alvarez F Anti-liver-kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily. J Exp Med 1988; 168:801.

    Article  Google Scholar 

  20. 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.

    PubMed  CAS  Google Scholar 

  21. Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type 2. Proc Natl Acad Sci USA 1988; 85:8256–8260.

    Article  PubMed  CAS  Google Scholar 

  22. Homberg JC, Andre C, Abuaf N. A new anti-liver/kidney-micro-some antibody (anti-LKM2) in tienilic induced hepatitis. Clin Exp Immunol 1984; 55:561–570.

    PubMed  CAS  Google Scholar 

  23. Crivelli O, Lavarini C, Chiaberge E, et al. Microsomal autoantibodies in chronic infection with HBsAg associated delta (delta) agent. Clin Exp Immunol 1983; 54:232–238.

    PubMed  CAS  Google Scholar 

  24. Philipp T, Durazzo M, Trautwein C, et al. Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 1994; 344:578–581.

    Article  PubMed  CAS  Google Scholar 

  25. Strassburg CP, Obermayer-Straub P, Alex B, et al. Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology 1996; 111:1576–1586.

    Article  PubMed  CAS  Google Scholar 

  26. Sugimura T, Obermayer-Straub P, Kayser A, et al. A major CYP2D6 autoepitope in autoimmune hepatitis type 2 and chronic hepatitis C is a three-dimensional structure homologous to other cytochrome P450 autoantigens. Autoimmunity 2002; 35:501–513.

    Article  PubMed  CAS  Google Scholar 

  27. Beaune PH, Lecoeur S, Bourdi M, et al. Anti-cytochrome P450 autoantibodies in drug-induced disease. Eur J Haematol Suppl 1996; 60:89–92.

    PubMed  CAS  Google Scholar 

  28. Belloc C, Gauffre A, Andre C, Beaune PH. Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis. Pharmacogenetics 1997; 7:181–186.

    Article  PubMed  CAS  Google Scholar 

  29. Clemente MG, Obermayer-Straub P, Meloni A, et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1997; 82: 1353–1361.

    Article  PubMed  CAS  Google Scholar 

  30. Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001; 120:1502–1517.

    Article  PubMed  CAS  Google Scholar 

  31. Strassburg CP, Obermayer-Straub P, Manns MP. Autoimmunity in liver diseases. Clin Rev Allergy Immunol 2000; 18:127–139.

    Article  PubMed  CAS  Google Scholar 

  32. Manns MP, Jentzsch M, Mergener K, et al. Discordant manifestation of LKM-1 antibody positive autoimmune hepatitis in identical twins. Hepatology 1990; 12:840.

    Article  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Dalekos GN, Wedemeyer H, Obermayer-Straub P, et al. Epitope mapping of cytochrome P4502D6 autoantigen in patients with chronic hepatitis C during alpha-interferon treatment. J Hepatol 1999; 30:366–375.

    Article  PubMed  CAS  Google Scholar 

  35. Strassburg CP, Manns MP. Autoimmune hepatitis versus viral hepatitis C. Liver 1995; 15:225–232.

    PubMed  CAS  Google Scholar 

  36. Durazzo M, Philipp T, Van Pelt FN, et al. Heterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection. Gastroenterology 1995; 108:455–462.

    Article  PubMed  CAS  Google Scholar 

  37. Dalekos GN, Obermayer-Straub P, Maeda T, Tsianos EV, Manns MR Antibodies against cytochrome P4502A6 (CYP2A6) in patients with chronic viral hepatitis are mainly linked to hepatitis C virus infection. Digestion 1998; 59:S36.

    Article  Google Scholar 

  38. Obermayer-Straub P, Braun S, Grams B, et al. Different liver cytochromes P450s are autoantigens in patients with autoimmune hepatitis and with autoimmune polyglandular syndrome type 1 (APS1). Hepatology 1996; 24(Suppl 4):429.

    Google Scholar 

  39. Philipp T, Straub P, Durazzo M, Tukey RH, Manns MP. Molecular analysis of autoantigens in hepatitis D. J Hepatol 1995; 22(Suppl 1): 132–135.

    PubMed  CAS  Google Scholar 

  40. Strassburg CP, Vogel A, Kneip S, Tukey RH, Manns MP. Polymorphisms of the UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer. Gut 2002; 50:851–856.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  42. Lankisch TO, Jaeckel E, Strassburg CP, Manns MP. [Autoimmune polyglandular syndromes]. Internist (Berl) 2005; 46:750–758.

    Article  CAS  Google Scholar 

  43. Vogel A, Strassburg CP, Obermayer-Straub P, Brabant G, Manns MP. The genetic background of autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy and its autoimmune disease components. Mol Med 2002; 80:201–210.

    Article  CAS  Google Scholar 

  44. Obermayer-Straub P, Perheentupa J, Braun S, et al. Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasisectodermal dystrophy. Gastroenterology 2001; 121:668–677.

    Article  PubMed  CAS  Google Scholar 

  45. Lankisch TO, Strassburg CP, Debray D, Manns MP, Jacquemin E. Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases. J Pediatr 2005; 146:839–842.

    Article  PubMed  CAS  Google Scholar 

  46. Vogel A, Liermann H, Harms A, Strassburg CP, Manns MP, Obermayer-Straub P. Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1. Hepatology 2001; 33:1047–1052.

    Article  PubMed  CAS  Google Scholar 

  47. Clot P, Albano E, Eliasson E, et al. Cytochrome P450 2E1 hydroxyethyl radical adducts as the major antigen in autoantibody formation among alcoholics. Gastroenterology 1996; 111:206–216.

    Article  PubMed  CAS  Google Scholar 

  48. Muratori L, Cataleta M, Muratori P, et al. Detection of anti-liver cytosol antibody type 1 (anti-LCI) by immunodiffusion, counterimmunoelectrophoresis and immunoblotting: comparison of different techniques. J Immunol Methods 1995; 187:259–264.

    Article  PubMed  CAS  Google Scholar 

  49. Lapierre P, Hajoui O, Homberg J-C, Alvarez F. Fomiminotransferase cyclodeaminase is an organ specific autoantigen recognized by sera of patients with autoimmune hepatitis. Gastroenterology 1999; 116:643–649.

    Article  PubMed  CAS  Google Scholar 

  50. Muratori L, Cataleta M, Muratori P, Lenzi M, Bianchi FB. Liver/ kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis. Gut 1998; 42:721–726.

    Article  PubMed  CAS  Google Scholar 

  51. Muratori L, Sztul E, Muratori P, et al. Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1. Hepatology 2001; 34:494–501.

    Article  PubMed  CAS  Google Scholar 

  52. Terjung B, Spengler U, Sauerbruch T, Worman HJ. “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology 2000; 119:310–322.

    Article  PubMed  CAS  Google Scholar 

  53. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999; 31:929–938.

    Article  PubMed  CAS  Google Scholar 

  54. Treichel U, Poralla T, Hess G, Manns M, Meyer zum Buschenfelde KH. Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatol 1990; 11:606–612.

    Article  CAS  Google Scholar 

  55. Joplin RE, Neuberger JM. Immunopathology of primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999; 11:587–593.

    Article  PubMed  CAS  Google Scholar 

  56. Lohr H, Fleischer B, Gerken G, Yeaman SJ, Meyer zum Buschenfelde KH, Manns M. Autoreactive liver-infiltrating T cells in primary biliary cirrhosis recognize inner mitochondrial epitopes and the pyruvate dehydrogenase complex. J Hepatol 1993; 18:322–327.

    Article  PubMed  CAS  Google Scholar 

  57. Van de Water J, Shimoda S, Niho Y, Coppel R, Ansari A, Gershwin ME. The role of T cells in primary biliary cirrhosis. Semin Liver Dis 1997; 17:105–113.

    Article  PubMed  Google Scholar 

  58. Mackay IR. Primary biliary cirrhosis showing a high titer of autoantibody. N Engl J Med 1958; 258:707–713.

    Article  Google Scholar 

  59. Berg PA, Doniach D, Roitt IM. Mitochondrial antibodies in primary biliary cirrhosis. I. Localization of the antigen to mitochondrial membranes. J Exp Med 1967; 126:277–290.

    Article  PubMed  CAS  Google Scholar 

  60. Berg PA, Klein R. Mitochondrial antigens and autoantibodies: from anti-Mi to anti-M9. Klin Wochenschr 1986; 64:897–909.

    Article  PubMed  CAS  Google Scholar 

  61. Frazer IH, Mackay IR, Jordan TW, Whittingham S, Marzuki S. Reactivity of anti-mitochondrial autoantibodies in primary biliary cirrhosis: definition of two novel mitochondrial polypeptide autoantigens. J Immunol 1985; 135:1739–1745.

    PubMed  CAS  Google Scholar 

  62. Ishii H, Saifuku K, Namihisa T. Multiplicity of mitochondrial inner membrane antigens from beef heart reacting with antimitochondrial antibodies in sera of patients with primary biliary cirrhosis. Immunol Lett 1985; 9:325–330.

    Article  PubMed  CAS  Google Scholar 

  63. Lindenborn-Fotinos J, Baum H, Berg PA. Mitochondrial antibodies in primary biliary cirrhosis: species and nonspecies specific determinants of M2 antigen. Hepatol 1985; 5:763–769.

    Article  CAS  Google Scholar 

  64. Manns M, Meyer zum Buschenfelde KH. A mitochondrial antigen-antibody system in cholestatic liver disease detected by radioimmunoassay. Hepatol 1982; 2:1–7.

    CAS  Google Scholar 

  65. Gershwin ME, Mackay IR, Sturgess A, Coppel RL. Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 1987; 138: 3525–3531.

    PubMed  CAS  Google Scholar 

  66. Gershwin ME, Mackay IR. Primary biliary cirrhosis: paradigm or paradox for autoimmunity. Gastroenterology 1991; 100:822–833.

    PubMed  CAS  Google Scholar 

  67. Van de Water J, Surh CD, Leung PS, et al. Molecular definitions, autoepitopes, and enzymatic activities of the mitochondrial autoantigens of primary biliary cirrhosis. Semin Liver Dis 1989; 9:132–137.

    PubMed  Google Scholar 

  68. Van de Water J, Gershwin ME, Leung P, Ansari A, Coppel RL The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase. J Exp Med 1988; 167:1791–1799.

    Article  PubMed  Google Scholar 

  69. Leung PS, Chuang DT, Wynn RM, et al. Autoantibodies to BCOADC-E2 in patients with primary biliary cirrhosis recognize a conformational epitope. Hepatology 1995; 22:505–513.

    PubMed  CAS  Google Scholar 

  70. Moteki S, Leung PS, Dickson ER, et al. Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex. Hepatology 1996; 23:436–444.

    Article  PubMed  CAS  Google Scholar 

  71. Fujimoto M, Sato S, Ihn H, Kikuchi K, Tamaki K, Takehara K. Autoantibodies to pyruvate dehydrogenase complex in patients with systemic sclerosis. Possible role of anti-E1 alpha antibody as a serologic indicator for development of primary biliary cirrhosis. Arthritis Rheum 1995; 38:985–989.

    Article  PubMed  CAS  Google Scholar 

  72. Leung PS, Van de Water J, Coppel RL, Nakanuma Y, Munoz S, Gershwin ME. Molecular aspects and the pathological basis of primary biliary cirrhosis. J Autoimmun 1996; 9:119–128.

    Article  PubMed  CAS  Google Scholar 

  73. Palmer JM, Jones DE, Quinn J, McHugh A, Yeaman SJ. Characterization of the autoantibody responses to recombinant E3 binding protein (protein X) of pyruvate dehydrogenase in primary biliary cirrhosis. Hepatology 1999; 30:21–26.

    Article  PubMed  CAS  Google Scholar 

  74. Nishio A, Van de Water J, Leung PS, et al. Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis. Hepatology 1997; 25:1085–1089.

    Article  PubMed  CAS  Google Scholar 

  75. Joplin R, Wallace LL, Johnson GD, et al. Subcellular localization of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in human intrahepatic biliary epithelial cells. J Pathol 1995; 176: 381–390.

    Article  PubMed  CAS  Google Scholar 

  76. Reynoso-Paz S, Leung PS, Van De Water J, et al. Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis. Hepatol 2000; 31: 24–29.

    Article  CAS  Google Scholar 

  77. Shimoda S, Van de Water J, Ansari A, et al. Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis. J Clin Invest 1998; 102:1831–1840.

    PubMed  CAS  Google Scholar 

  78. Shimoda S, Nakamura M, Shigematsu H, et al. Mimicry peptides of human PDC-E2 163–176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis. Hepatology 2000; 31:1212–1216.

    Article  PubMed  CAS  Google Scholar 

  79. Kita H, Lian ZX, Van de Water J, et al. Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells. J Exp Med 2002; 195:113–123.

    Article  PubMed  CAS  Google Scholar 

  80. Kita H, Matsumura S, He XS, et al. Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. J Clin Invest 2002; 109:1231–1240.

    Article  PubMed  CAS  Google Scholar 

  81. Bloch DB, Chiche JD, Orth D, de la Monte SM, Rosenzweig A, Bloch KD. Structural and functional heterogeneity of nuclear bodies. Mol Cell Biol 1999; 19:4423–4430.

    PubMed  CAS  Google Scholar 

  82. Worman HJ. Primary biliary cirrhosis and the molecular cell biology of the nuclear envelope. Mt Sinai J Med 1994; 61:461–475.

    PubMed  CAS  Google Scholar 

  83. Lassoued K, Brenard R, Degos F, et al. Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis. Gastroenterology 1990; 99:181–186.

    PubMed  CAS  Google Scholar 

  84. Nickowitz RE, Wozniak RW, Schaffner F, Worman HJ. Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis. Gastroenterology 1994; 106:193–199.

    PubMed  CAS  Google Scholar 

  85. Dubel L, Farges O, Courvalin JC, Sebagh M, Johanet C. Persistence of gp210 and multiple nuclear dots antibodies does not correlate with recurrence of primary biliary cirrhosis 6 years after liver transplantation [letter]. J Hepatol 1998; 28:169–170.

    Article  PubMed  CAS  Google Scholar 

  86. Luettig B, Boeker KH, Schoessler W, et al. The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis. J Hepatol 1998; 28:824–828.

    Article  PubMed  CAS  Google Scholar 

  87. Mattalia A, Luttig B, Rosina F, et al. Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis. J Autoimmun 1997; 10:491–497.

    Article  PubMed  CAS  Google Scholar 

  88. Nickowitz RE, Worman HJ. Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210. J Exp Med 1993; 178:2237–2242.

    Article  PubMed  CAS  Google Scholar 

  89. Wesierska-Gadek J, Hohenuer H, Hitchman E, Penner E. Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis. Gastroenterology 1996; 110:840–847.

    Article  PubMed  CAS  Google Scholar 

  90. Szostecki C, Will H, Netter HJ, Guldner HH. Autoantibodies to the nuclear Sp100 protein in primary biliary cirrhosis and associated diseases: epitope specificity and immunoglobulin class distribution. Scand J Immunol 1992; 36:555–564.

    Article  PubMed  CAS  Google Scholar 

  91. Zuchner D, Sternsdorf T, Szostecki C, Heathcote EJ, Cauch-Dudek K, Will H. Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatol 1997; 26:1123–1130.

    CAS  Google Scholar 

  92. Bluthner M, Schafer C, Schneider C, Bautz FA. Identification of major linear epitopes on the sp100 nuclear PBC autoantigen by the genefragment phage-display technology. Autoimmunity 1999; 29:33–42.

    Article  PubMed  CAS  Google Scholar 

  93. Lin F, Noyer CM, Ye Q, Courvalin JC, Worman HJ. Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR Hepatology 1996; 23:57–61.

    Article  CAS  Google Scholar 

  94. Sternsdorf T, Guldner HH, Szostecki C, Grotzinger T, Will H. Two nuclear dot-associated proteins, PML and Sp100, are often co-autoimmunogenic in patients with primary biliary cirrhosis. Scand J Immunol 1995; 42:257–268.

    Article  PubMed  CAS  Google Scholar 

  95. Strassburg CP, Manns MP Primary biliary liver cirrhosis and overlap syndrome. Diagnosis and therapy. Internist (Berl) 2004; 45:16–26.

    Article  CAS  Google Scholar 

  96. Vogel A, Wedemeyer H, M PM, Strassburg CP. Autoimmune hepatitis and overlap syndromes. J Gastroenterol Hepatol 2002; 17(Suppl 3):S389–S398.

    Article  PubMed  Google Scholar 

  97. Goodman ZD, McNally PR, Davis DR, Ishak KG. Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases. Dig Dis Sci 1995; 40:1232–1242.

    Article  PubMed  CAS  Google Scholar 

  98. Ben-Ari Z, Dhillon AP, Sherlock S. Autoimmune cholangiopathy: part of the spectrum of autoimmune chronic active hepatitis. Hepatology 1993; 18:10–15.

    PubMed  CAS  Google Scholar 

  99. Michieletti P, Wanless IR, Katz A, et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut 1994; 35:260–265.

    Article  PubMed  CAS  Google Scholar 

  100. Colombato LA, Alvarez F, Cote J, Huet PM. Autoimmune cholangiopathy: the result of consecutive primary biliary cirrhosis and autoimmune hepatitis? Gastroenterology 1994; 107:1839–1843.

    PubMed  CAS  Google Scholar 

  101. Kiyosawa K, Daemer RJ, He LF, Bonino F, Prozesky OW, Purcell RH. The spectrum of complement-fixing antinuclear antibodies in patients with hepatocellular carcinoma. Hepatology 1985; 5:548–555.

    Article  PubMed  CAS  Google Scholar 

  102. Forbes AP, Lake JR, Bloch KJ. Circulating antibody to renal collecting ducts in patients with hepatoma or renal-cell carcinoma. Clin Exp Immunol 1975; 22:426–430.

    PubMed  CAS  Google Scholar 

  103. Walcher J, Witter T, Rupprecht HD. Hepatocellular carcinoma presenting with paraneoplastic demyelinating polyneuropathy and PR3-antineutrophil cytoplasmic antibody. J Clin Gastroenterol 2002; 35:364–365.

    Article  PubMed  CAS  Google Scholar 

  104. Zhang J, Chan EK. Autoantibodies to IGF-II mRNA binding protein p62 and overexpression of p62 in human hepatocellular carcinoma. Autoimmun Rev 2002; 1:146–153.

    Article  PubMed  CAS  Google Scholar 

  105. Covini G, von Muhlen CA, Pacchetti S, Colombo M, Chan EK, Tan EM. Diversity of antinuclear antibody responses in hepatocellular carcinoma. J Hepatol 1997; 26:1255–1265.

    Article  PubMed  CAS  Google Scholar 

  106. Raedle J, Oremek G, Truschnowitsch M, et al. Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma. Eur J Cancer 1998; 34:1198–1203.

    Article  PubMed  CAS  Google Scholar 

  107. Masutomi K, Kaneko S, Yasukawa M, Arai K, Murakami S, Kobayashi K. Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma. Oncogene 2002; 21:5946–5950.

    Article  PubMed  CAS  Google Scholar 

  108. Covini G, Chan EK, Nishioka M, Morshed SA, Reed SI, Tan EM. Immune response to cyclin B1 in hepatocellular carcinoma. Hepatology 1997; 25:75–80.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

    Christian P. Strassburg MD & Michael P. Manns MD

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  1. Christian P. Strassburg MD
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Editors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA

    M. Eric Gershwin MD, FACP

  2. Departments of Medicine and Surgery Baylor Liver Health, Baylor College of Medicine, Houston, TX

    John M. Vierling MD, FACP

  3. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Hannover, Germany

    Michael P. Manns MD

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Strassburg, C.P., Manns, M.P. (2007). Prevalence and Significance of Autoantibodies in Acute and Chronic Liver Diseases and Hepatocellular Carcinoma. In: Gershwin, M.E., Vierling, J.M., Manns, M.P. (eds) Liver Immunology. Humana Press. https://doi.org/10.1007/978-1-59745-518-3_9

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  • DOI: https://doi.org/10.1007/978-1-59745-518-3_9

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-818-8

  • Online ISBN: 978-1-59745-518-3

  • eBook Packages: MedicineMedicine (R0)

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