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Autoantibodies as Prognostic Markers in Autoimmune Liver Disease

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Abstract

Certain autoantibodies in autoimmune liver disease have prognostic implications that are under-utilized and under-developed. The goals of this review are to indicate progress in characterizing the autoantibodies with prognostic connotations and to indicate the feasibility and importance of discovering other markers. Prime source and review articles in English were selected by a Medline search through 2010. Antibodies to soluble liver antigen, actin, liver cytosol type 1, asialoglycoprotein receptor, chromatin, cyclic citrullinated peptide, and uridine glucuronosyltransferases have been associated with the occurrence, severity, and progression of autoimmune hepatitis, and antibodies to Sp100, gp210, and centromere have had similar implications in primary biliary cirrhosis. Antibodies to soluble liver antigen have shown the most promise in autoimmune hepatitis as they have been associated with severe histological changes, long durations of treatment, relapse after drug withdrawal, and high frequency of liver failure. Antibodies to the nuclear rim pore protein, gp210, have shown the most promise in primary biliary cirrhosis as they have been associated with severe interface hepatitis, lobular inflammation, and progression to liver failure. The major limitations of the autoantibodies have been their lack of standardized assays, low negative predictabilities, and fluctuating levels. Performance parameters will improve as critical pathogenic pathways, comprehensive testing batteries, and standardized assays through international exchange workshops are developed. Progress has been made in identifying the serological markers of prognosis in autoimmune liver disease, and they promise to reflect critical disease mechanisms and enhance patient management.

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References

  1. Bogdanos DP, Mieli-Vergani G, Vergani D. Autoantibodies and their antigens in autoimmune hepatitis. Semin Liver Dis. 2009;29:241–253.

    CAS  PubMed  Google Scholar 

  2. Czaja AJ, Nishioka M, Morshed SA, Hachiya T. Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis. Gastroenterology. 1994;107:200–207.

    CAS  PubMed  Google Scholar 

  3. Czaja AJ, Cassani F, Cataleta M, Valentini P, Bianchi FB. Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis. Dig Dis Sci. 1997;42:1688–1696.

    CAS  PubMed  Google Scholar 

  4. Toh BH. Smooth muscle autoantibodies and autoantigens. Clin Exp Immunol. 1979;38:621–628.

    CAS  PubMed  Google Scholar 

  5. 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.

    CAS  PubMed  Google Scholar 

  6. Czaja AJ. Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance. Liver Transpl. 2002;8:505–513.

    PubMed  Google Scholar 

  7. Czaja AJ. Autoantibodies in autoimmune liver disease. Adv Clin Chem. 2005;40:127–164.

    CAS  PubMed  Google Scholar 

  8. Manns MP, Czaja AJ, Gorham JD, et al. Practice Guidelines of the American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. (in press).

  9. Van de Water J, Cooper A, Surh CD, et al. Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med. 1989;320:1377–1380.

    PubMed  Google Scholar 

  10. Fregeau DR, Davis PA, Danner DJ, et al. Antimitochondrial antibodies of primary biliary cirrhosis recognize dihydrolipoamide acyltransferase and inhibit enzyme function of the branched chain alpha-ketoacid dehydrogenase complex. J Immunol. 1989;142:3815–3820.

    CAS  PubMed  Google Scholar 

  11. Lindor KD, Gershwin ME, Poupon R, et al. AASLD practice guidelines. Primary biliary cirrhosis. Hepatology. 2009;50:291–308.

    PubMed  Google Scholar 

  12. Homberg JC, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of “autoimmune” hepatitis. Hepatology. 1987;7:1333–1339.

    CAS  PubMed  Google Scholar 

  13. Czaja AJ, Manns MP, Homburger HA. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology. 1992;103:1290–1295.

    CAS  PubMed  Google Scholar 

  14. Czaja AJ, Manns MP. The validity and importance of subtypes in autoimmune hepatitis: a point of view. Am J Gastroenterol. 1995;90:1206–1211.

    CAS  PubMed  Google Scholar 

  15. Bittencourt PL, Goldberg AC, Cancado EL, et al. Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2. Am J Gastroenterol. 1999;94:1906–1913.

    CAS  PubMed  Google Scholar 

  16. Czaja AJ, Kruger M, Santrach PJ, Moore SB, Manns MP. Genetic distinctions between types 1 and 2 autoimmune hepatitis. Am J Gastroenterol. 1997;92:2197–2200.

    CAS  PubMed  Google Scholar 

  17. Muratori P, Czaja AJ, Muratori L, et al. Genetic distinctions between autoimmune hepatitis in Italy and North America. World J Gastroenterol. 2005;11:1862–1866.

    PubMed  Google Scholar 

  18. Strettell MD, Donaldson PT, Thomson LJ, et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology. 1997;112:2028–2035.

    CAS  PubMed  Google Scholar 

  19. Czaja AJ, Strettell MD, Thomson LJ, et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology. 1997;25:317–323.

    CAS  PubMed  Google Scholar 

  20. Djilali-Saiah I, Renous R, Caillat-Zucman S, Debray D, Alvarez F. Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients. J Hepatol. 2004;40:904–909.

    CAS  PubMed  Google Scholar 

  21. Gregorio GV, Portmann B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997;25:541–547.

    CAS  PubMed  Google Scholar 

  22. Czaja AJ. Behavior and significance of autoantibodies in type 1 autoimmune hepatitis. J Hepatol. 1999;30:394–401.

    CAS  PubMed  Google Scholar 

  23. Luth S, Herkel J, Kanzler S, et al. Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis. J Clin Gastroenterol. 2008;42:926–930.

    PubMed  Google Scholar 

  24. Heseltine L, Turner IB, Fussey SP, et al. Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. Gastroenterology. 1990;99:1786–1792.

    CAS  PubMed  Google Scholar 

  25. Van Norstrand MD, Malinchoc M, Lindor KD, et al. Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression. Hepatology. 1997;25:6–11.

    PubMed  Google Scholar 

  26. Lazaridis KN, Juran BD, Boe GM, et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology. 2007;46:785–792.

    PubMed  Google Scholar 

  27. Gershwin ME, Ansari AA, Mackay IR, et al. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells. Immunol Rev. 2000;174:210–225.

    CAS  PubMed  Google Scholar 

  28. Senecal JL, Ichiki S, Girard D, Raymond Y. Autoantibodies to nuclear lamins and to intermediate filament proteins: natural, pathologic or pathogenic? J Rheumatol. 1993;20:211–219.

    CAS  PubMed  Google Scholar 

  29. Czaja AJ. Autoantibodies. Baillieres Clin Gastroenterol. 1995;9:723–744.

    CAS  PubMed  Google Scholar 

  30. Meyers KE, Christensen M, Madaio MP. Modeling of human anti-GBM antibody-alpha3(IV)NC1 interactions predicts antigenic cross-linking through contact of both heavy chains with repeating epitopes on alpha3(IV)NC1. Am J Nephrol. 2009;30:474–480.

    CAS  PubMed  Google Scholar 

  31. Zhao J, Cui Z, Yang R, et al. Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity. Kidney Int. 2009;76:1108–1115.

    CAS  PubMed  Google Scholar 

  32. Manns M, Zanger U, Gerken G, et al. Patients with type II autoimmune hepatitis express functionally intact cytochrome P-450 db1 that is inhibited by LKM-1 autoantibodies in vitro but not in vivo. Hepatology. 1990;12:127–132.

    CAS  PubMed  Google Scholar 

  33. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB, Homburger HA. The nature and prognosis of severe cryptogenic chronic active hepatitis. Gastroenterology. 1993;104:1755–1761.

    CAS  PubMed  Google Scholar 

  34. Gassert DJ, Garcia H, Tanaka K, Reinus JF. Corticosteroid-responsive cryptogenic chronic hepatitis: evidence for seronegative autoimmune hepatitis. Dig Dis Sci. 2007;52:2433–2437.

    CAS  PubMed  Google Scholar 

  35. Heringlake S, Schutte A, Flemming P, et al. Presumed cryptogenic liver disease in Germany: high prevalence of autoantibody-negative autoimmune hepatitis, low prevalence of NASH, no evidence for occult viral etiology. Z Gastroenterol. 2009;47:417–423.

    CAS  PubMed  Google Scholar 

  36. Lacerda MA, Ludwig J, Dickson ER, Jorgensen RA, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995;90:247–249.

    CAS  PubMed  Google Scholar 

  37. Invernizzi P, Crosignani A, Battezzati PM, et al. Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology. 1997;25:1090–1095.

    CAS  PubMed  Google Scholar 

  38. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  41. Ballot E, Homberg JC, Johanet C. Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis. J Hepatol. 2000;33:208–215.

    CAS  PubMed  Google Scholar 

  42. Baeres M, Herkel J, Czaja AJ, et al. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut. 2002;51:259–264.

    CAS  PubMed  Google Scholar 

  43. Czaja AJ, Shums Z, Norman GL. Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis. Autoimmunity. 2002;35:475–483.

    CAS  PubMed  Google Scholar 

  44. Eyraud V, Chazouilleres O, Ballot E, et al. Significance of antibodies to soluble liver antigen/liver pancreas: a large French study. Liver Int. 2009;29:857–864.

    CAS  PubMed  Google Scholar 

  45. Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology. 1993;105:1522–1528.

    CAS  PubMed  Google Scholar 

  46. Kanzler S, Weidemann C, Gerken G, et al. Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis. J Hepatol. 1999;31:635–640.

    CAS  PubMed  Google Scholar 

  47. Vitozzi S, Djilali-Saiah I, Lapierre P, Alvarez F. Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis. Autoimmunity. 2002;35:485–492.

    CAS  PubMed  Google Scholar 

  48. Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology (in press).

  49. Torres-Collado AX, Czaja AJ, Gelpi C. Anti-tRNP(ser)sec/SLA/LP autoantibodies. Comparative study using in-house ELISA with a recombinant 48.8-kDa protein, immunoblot, and analysis of immunoprecipitated RNAs. Liver Int. 2005;25:410–419.

    CAS  PubMed  Google Scholar 

  50. Ma Y, Okamoto M, Thomas MG, et al. Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology. 2002;35:658–664.

    CAS  PubMed  Google Scholar 

  51. Czaja AJ, Donaldson PT, Lohse AW. Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis. Am J Gastroenterol. 2002;97:413–419.

    PubMed  Google Scholar 

  52. Seki T, Ota M, Furuta S, et al. HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients. Gastroenterology. 1992;103:1041–1047.

    CAS  PubMed  Google Scholar 

  53. Yoshizawa K, Ota M, Katsuyama Y, et al. Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis. J Hepatol. 2005;42:578–584.

    CAS  PubMed  Google Scholar 

  54. Miyakawa H, Kawashima Y, Kitazawa E, et al. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay. J Autoimmun. 2003;21:77–82.

    CAS  PubMed  Google Scholar 

  55. Vitozzi S, Lapierre P, Djilali-Saiah I, et al. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection. Autoimmunity. 2004;37:217–222.

    CAS  PubMed  Google Scholar 

  56. Rigopoulou EI, Mytilinaiou M, Romanidou O, Liaskos C, Dalekos GN. Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis. J Autoimmune Dis. 2007;4:2.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  58. Volkmann M, Martin L, Baurle A, et al. Soluble liver antigen: isolation of a 35-kD recombinant protein (SLA-p35) specifically recognizing sera from patients with autoimmune hepatitis. Hepatology. 2001;33:591–596.

    CAS  PubMed  Google Scholar 

  59. Costa M, Rodriguez-Sanchez JL, Czaja AJ, Gelpi C. Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis. Clin Exp Immunol. 2000;121:364–374.

    CAS  PubMed  Google Scholar 

  60. Herkel J, Heidrich B, Nieraad N, et al. Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas. Hepatology. 2002;35:403–408.

    CAS  PubMed  Google Scholar 

  61. Mix H, Weiler-Normann C, Thimme R, et al. Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis. Gastroenterology. 2008;135:2107–2118.

    CAS  PubMed  Google Scholar 

  62. 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.

    CAS  PubMed  Google Scholar 

  63. Muratori P, Muratori L, Agostinelli D, et al. Smooth muscle antibodies and type 1 autoimmune hepatitis. Autoimmunity. 2002;35:497–500.

    CAS  PubMed  Google Scholar 

  64. Granito A, Muratori L, Muratori P, et al. Antibodies to filamentous actin (F-actin) in type 1 autoimmune hepatitis. J Clin Pathol. 2006;59:280–284.

    CAS  PubMed  Google Scholar 

  65. Fusconi M, Cassani F, Zauli D, et al. Anti-actin antibodies: a new test for an old problem. J Immunol Methods. 1990;130:1–8.

    CAS  PubMed  Google Scholar 

  66. Chretien-Leprince P, Ballot E, Andre C, et al. Diagnostic value of anti-F-actin antibodies in a French multicenter study. Ann NY Acad Sci. 2005;1050:266–273.

    CAS  PubMed  Google Scholar 

  67. Bottazzo GF, Florin-Christensen A, Fairfax A, et al. Classification of smooth muscle autoantibodies detected by immunofluorescence. J Clin Pathol. 1976;29:403–410.

    CAS  PubMed  Google Scholar 

  68. Soares A, Cunha R, Rodrigues F, Ribeiro H. Smooth muscle autoantibodies with F-actin specificity. Autoimmun Rev. 2009;8:713–716.

    CAS  PubMed  Google Scholar 

  69. Aubert V, Pisler IG, Spertini F. Improved diagnoses of autoimmune hepatitis using an anti-actin ELISA. J Clin Lab Anal. 2008;22:340–345.

    PubMed  Google Scholar 

  70. Frenzel C, Herkel J, Luth S, et al. Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis. Am J Gastroenterol. 2006;101:2731–2736.

    CAS  PubMed  Google Scholar 

  71. Martinez-Neira R, dos Remedios CG, Mackay IR. An actin-myosin functional assay for analysis of smooth muscle (anti-microfilament) autoantibodies in human plasma. J Immunol Methods. 2008;338:63–66.

    CAS  PubMed  Google Scholar 

  72. Cancado EL, Abrantes-Lemos CP, Vilas-Boas LS, et al. Thermolabile and calcium-dependent serum factor interferes with polymerized actin, and impairs anti-actin antibody detection. J Autoimmun. 2001;17:223–228.

    CAS  PubMed  Google Scholar 

  73. Villalta D, Bizzaro N, Da Re M, et al. Diagnostic accuracy of four different immunological methods for the detection of anti-F-actin autoantibodies in type 1 autoimmune hepatitis and other liver-related disorders. Autoimmunity. 2008;41:105–110.

    CAS  PubMed  Google Scholar 

  74. Toh BH, Taylor R, Pollock W. F-actin reactive smooth muscle antibody in subjects with normal liver function. Pathology. 2009;41:572–575.

    PubMed  Google Scholar 

  75. Jaskowski TD, Konnick EQ, Ashwood ER, Litwin CM, Hill HR. Prevalence of IgG autoantibody against F-actin in patients suspected of having autoimmune or acute viral hepatitis. J Clin Lab Anal. 2007;21:249–253.

    CAS  PubMed  Google Scholar 

  76. Zamanou A, Samiotaki M, Panayotou G, Margaritis L, Lymberi P. Fine specificity and subclasses of IgG anti-actin autoantibodies differ in health and disease. J Autoimmun. 2003;20:333–344.

    CAS  PubMed  Google Scholar 

  77. Maggiore G, Veber F, Bernard O, et al. Autoimmune hepatitis associated with anti-actin antibodies in children and adolescents. J Pediatr Gastroenterol Nutr. 1993;17:376–381.

    Article  CAS  PubMed  Google Scholar 

  78. Czaja AJ, Cassani F, Cataleta M, Valentini P, Bianchi FB. Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis. Hepatology. 1996;24:1068–1073.

    CAS  PubMed  Google Scholar 

  79. Gueguen P, Dalekos G, Nousbaum JB, et al. Double reactivity against actin and alpha-actinin defines a severe form of autoimmune hepatitis type 1. J Clin Immunol. 2006;26:495–505.

    PubMed  Google Scholar 

  80. Renaudineau Y, Dalekos GN, Gueguen P, Zachou K, Youinou P. Anti-alpha-actinin antibodies cross-react with anti-ssDNA antibodies in active autoimmune hepatitis. Clin Rev Allergy Immunol. 2008;34:321–325.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  82. 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.

    CAS  PubMed  Google Scholar 

  83. Renous R, Lapierre P, Djilali-Saiah I, Vitozzi S, Alvarez F. Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis. Exp Cell Res. 2004;292:332–341.

    CAS  PubMed  Google Scholar 

  84. Lapierre P, Johanet C, Alvarez F. Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis. Eur J Immunol. 2003;33:1869–1878.

    CAS  PubMed  Google Scholar 

  85. 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  CAS  PubMed  Google Scholar 

  86. Martini E, Abuaf N, Cavalli F, et al. Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology. 1988;8:1662–1666.

    CAS  PubMed  Google Scholar 

  87. Abuaf N, Johanet C, Chretien P, et al. Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. Hepatology. 1992;16:892–898.

    CAS  PubMed  Google Scholar 

  88. Muratori L, Cataleta M, Muratori P, et al. Detection of anti-liver cytosol antibody type 1 (anti-LC1) by immunodiffusion, counterimmunoelectrophoresis and immunoblotting: comparison of different techniques. J Immunol Methods. 1995;187:259–264.

    CAS  PubMed  Google Scholar 

  89. Bridoux-Henno L, Maggiore G, Johanet C, et al. Features and outcome of autoimmune hepatitis type 2 presenting with isolated positivity for anti-liver cytosol antibody. Clin Gastroenterol Hepatol.. 2004;2:825–830.

    PubMed  Google Scholar 

  90. Han S, Tredger M, Gregorio GV, Mieli-Vergani G, Vergani D. Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease. Hepatology. 1995;21:58–62.

    CAS  PubMed  Google Scholar 

  91. Lenzi M, Manotti P, Muratori L, et al. Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. Gut. 1995;36:749–754.

    CAS  PubMed  Google Scholar 

  92. Ballot E, Desbos A, Monier JC. Detection on immunoblot of new proteins from the soluble fraction of the cell recognized either by anti-liver-kidney microsome antibodies type 1 or by anti-liver cytosol antibodies type 1–relationship with hepatitis C virus infection. Clin Immunol Immunopathol. 1996;80:245–254.

    CAS  PubMed  Google Scholar 

  93. Beland K, Lapierre P, Marceau G, Alvarez F. Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection. J Autoimmun. 2004;22:159–166.

    CAS  PubMed  Google Scholar 

  94. Czaja AJ, Shums Z, Norman GL. Nonstandard antibodies as prognostic markers in autoimmune hepatitis. Autoimmunity. 2004;37:195–201.

    CAS  PubMed  Google Scholar 

  95. McFarlane IG, McFarlane BM, Major GN, Tolley P, Williams R. Identification of the hepatic asialo-glycoprotein receptor (hepatic lectin) as a component of liver specific membrane lipoprotein (LSP). Clin Exp Immunol. 1984;55:347–354.

    CAS  PubMed  Google Scholar 

  96. Poralla T, Treichel U, Lohr H, Fleischer B. The asialoglycoprotein receptor as target structure in autoimmune liver diseases. Semin Liver Dis. 1991;11:215–222.

    CAS  PubMed  Google Scholar 

  97. Enrich C, Verges M, Evans WH. Differential expression of asialoglycoprotein receptor subunits in the endocytic compartment during liver regeneration. J Cell Physiol. 1992;150:344–352.

    CAS  PubMed  Google Scholar 

  98. Hajoui O, Martin S, Alvarez F. Study of antigenic sites on the asialoglycoprotein receptor recognized by autoantibodies. Clin Exp Immunol. 1998;113:339–345.

    CAS  PubMed  Google Scholar 

  99. Schreiter T, Liu C, Gerken G, Treichel U. Detection of circulating autoantibodies directed against the asialoglycoprotein receptor using recombinant receptor subunit H1. J Immunol Methods. 2005;301:1–10.

    CAS  PubMed  Google Scholar 

  100. Mizuno M, Kloppel TM, Nakane PK, Brown WR, Vierling JM. Cellular distribution of the asialoglycoprotein receptor in rat liver. Implications for hepatic accumulation of desialylated lymphocytes. Gastroenterology. 1984;86:142–149.

    CAS  PubMed  Google Scholar 

  101. Mizuno M, Brown WR, Vierling JM. Ultrastructural immunocytochemical localization of the asialoglycoprotein receptor in rat hepatocytes. Gastroenterology. 1984;87:763–769.

    CAS  PubMed  Google Scholar 

  102. Henis YI, Katzir Z, Shia MA, Lodish HF. Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing H1 and H2 polypeptides assessed by fluorescence photobleaching recovery. J Cell Biol. 1990;111:1409–1418.

    CAS  PubMed  Google Scholar 

  103. Park JH, Kim KL, Cho EW. Detection of surface asialoglycoprotein receptor expression in hepatic and extra-hepatic cells using a novel monoclonal antibody. Biotechnol Lett. 2006;28:1061–1069.

    CAS  PubMed  Google Scholar 

  104. Meyer zum Buschenfelde KH, Treichel U, Lohr H, Fleischer B, Poralla T. Human asialoglycoprotein receptor as an autoantigen in chronic hepatitis. Immunol Res. 1991;10:497–502.

    CAS  PubMed  Google Scholar 

  105. McFarlane BM, McSorley CG, Vergani D, McFarlane IG, Williams R. Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. J Hepatol. 1986;3:196–205.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  107. Treichel U, Gerken G, Rossol S, et al. Autoantibodies against the human asialoglycoprotein receptor: effects of therapy in autoimmune and virus-induced chronic active hepatitis. J Hepatol. 1993;19:55–63.

    CAS  PubMed  Google Scholar 

  108. Treichel U, McFarlane BM, Seki T, et al. Demographics of anti-asialoglycoprotein receptor autoantibodies in autoimmune hepatitis. Gastroenterology. 1994;107:799–804.

    CAS  PubMed  Google Scholar 

  109. Husa P, Chalupa P, Stroblova H, et al. Autoantibodies to asialoglycoprotein receptor in chronic hepatitis C patients. Acta Virol. 2001;45:7–11.

    CAS  PubMed  Google Scholar 

  110. Yoshioka M, Mizuno M, Morisue Y, et al. Anti-asialoglycoprotein receptor autoantibodies, detected by a capture-immunoassay, are associated with autoimmune liver diseases. Acta Med Okayama. 2002;56:99–105.

    CAS  PubMed  Google Scholar 

  111. Hajoui O, Debray D, Martin S, Alvarez F. Auto-antibodies to the asialoglycoprotein receptor in sera of children with auto-immune hepatitis. Eur J Pediatr. 2000;159:310–313.

    CAS  PubMed  Google Scholar 

  112. 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.

    CAS  PubMed  Google Scholar 

  113. Lohr H, Treichel U, Poralla T, et al. The human hepatic asialoglycoprotein receptor is a target antigen for liver-infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis. Hepatology. 1990;12:1314–1320.

    CAS  PubMed  Google Scholar 

  114. Lohr H, Treichel U, Poralla T, Manns M, Meyer zum Buschenfelde KH. Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro. Clin Exp Immunol. 1992;88:45–49.

    Article  CAS  PubMed  Google Scholar 

  115. Kakegawa T, Ise H, Sugihara N, et al. Soluble asialoglycoprotein receptors reflect the apoptosis of hepatocytes. Cell Transplant. 2002;11:407–415.

    PubMed  Google Scholar 

  116. McFarlane BM, Sipos J, Gove CD, McFarlane IG, Williams R. Antibodies against the hepatic asialoglycoprotein receptor perfused in situ preferentially attach to periportal liver cells in the rat. Hepatology. 1990;11:408–415.

    CAS  PubMed  Google Scholar 

  117. Hilgard P, Schreiter T, Stockert RJ, Gerken G, Treichel U. Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis. Hepatology. 2004;39:1398–1407.

    CAS  PubMed  Google Scholar 

  118. Diao J, Michalak TI. Virus-induced anti-asialoglycoprotein receptor autoimmunity in experimental hepadnaviral hepatitis. Hepatology. 1997;25:689–696.

    CAS  PubMed  Google Scholar 

  119. Inamoto T, Brown WR. IgG is associated with the asialoglycoprotein receptor in the human liver. Hepatology. 1991;14:1070–1075.

    CAS  PubMed  Google Scholar 

  120. Czaja AJ, Pfeifer KD, Decker RH, Vallari AS. Frequency and significance of antibodies to asialoglycoprotein receptor in type 1 autoimmune hepatitis. Dig Dis Sci. 1996;41:1733–1740.

    CAS  PubMed  Google Scholar 

  121. McFarlane IG, Hegarty JE, McSorley CG, McFarlane BM, Williams R. Antibodies to liver-specific protein predict outcome of treatment withdrawal in autoimmune chronic active hepatitis. Lancet. 1984;2:954–956.

    CAS  PubMed  Google Scholar 

  122. Dejica D, Treichel U, Par A, Chira O, Meyer zum Buschenfelde KH. Anti asialoglycoprotein receptor antibodies and soluble interleukin-2 receptor levels as marker for inflammation in autoimmune hepatitis. Z Gastroenterol. 1997;35:15–21.

    CAS  PubMed  Google Scholar 

  123. Hausdorf G, Roggenbuck D, Feist E, et al. Autoantibodies to asialoglycoprotein receptor (ASGPR) measured by a novel ELISA—revival of a disease-activity marker in autoimmune hepatitis. Clin Chim Acta. 2009;408:19–24.

    CAS  PubMed  Google Scholar 

  124. Mohan C, Adams S, Stanik V, Datta SK. Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med. 1993;177:1367–1381.

    CAS  PubMed  Google Scholar 

  125. Doenecke D, Albig W, Bode C, et al. Histones: genetic diversity and tissue-specific gene expression. Histochem Cell Biol. 1997;107:1–10.

    CAS  PubMed  Google Scholar 

  126. Burlingame RW, Cervera R. Anti-chromatin (anti-nucleosome) autoantibodies. Autoimmun Rev. 2002;1:321–328.

    CAS  PubMed  Google Scholar 

  127. Amoura Z, Koutouzov S, Piette JC. The role of nucleosomes in lupus. Curr Opin Rheumatol. 2000;12:369–373.

    CAS  PubMed  Google Scholar 

  128. Amoura Z, Chabre H, Koutouzov S, et al. Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria. Arthritis Rheum. 1994;37:1684–1688.

    CAS  PubMed  Google Scholar 

  129. Burlingame RW, Boey ML, Starkebaum G, Rubin RL. The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. J Clin Invest. 1994;94:184–192.

    CAS  PubMed  Google Scholar 

  130. Li L, Chen M, Huang DY, Nishioka M. Frequency and significance of antibodies to chromatin in autoimmune hepatitis type I. J Gastroenterol Hepatol. 2000;15:1176–1182.

    CAS  PubMed  Google Scholar 

  131. Czaja AJ, Shums Z, Binder WL, et al. Frequency and significance of antibodies to chromatin in autoimmune hepatitis. Dig Dis Sci. 2003;48:1658–1664.

    CAS  PubMed  Google Scholar 

  132. El-Din Elshazly LB, Youssef AM, Mahmoud NH, Ibrahim MM. Study of nonstandard auto-antibodies as prognostic markers in auto immune hepatitis in children. Ital J Pediatr. 2009;35:22.

    PubMed  Google Scholar 

  133. Penner E. Nature of immune complexes in autoimmune chronic active hepatitis. Gastroenterology. 1987;92:304–308.

    CAS  PubMed  Google Scholar 

  134. Konikoff F, Swissa M, Shoenfeld Y. Autoantibodies to histones and their subfractions in chronic liver diseases. Clin Immunol Immunopathol. 1989;51:77–82.

    CAS  PubMed  Google Scholar 

  135. Czaja AJ, Ming C, Shirai M, Nishioka M. Frequency and significance of antibodies to histones in autoimmune hepatitis. J Hepatol. 1995;23:32–38.

    CAS  PubMed  Google Scholar 

  136. Chen M, Shirai M, Czaja AJ, et al. Characterization of anti-histone antibodies in patients with type 1 autoimmune hepatitis. J Gastroenterol Hepatol. 1998;13:483–489.

    CAS  PubMed  Google Scholar 

  137. Czaja AJ, Morshed SA, Parveen S, Nishioka M. Antibodies to single-stranded and double-stranded DNA in antinuclear antibody-positive type 1-autoimmune hepatitis. Hepatology. 1997;26:567–572.

    CAS  PubMed  Google Scholar 

  138. Nijenhuis S, Zendman AJ, Vossenaar ER, Pruijn GJ, vanVenrooij WJ. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker. Clin Chim Acta. 2004;350:17–34.

    CAS  PubMed  Google Scholar 

  139. Zendman AJ, Vossenaar ER, van Venrooij WJ. Autoantibodies to citrullinated (poly)peptides: a key diagnostic and prognostic marker for rheumatoid arthritis. Autoimmunity. 2004;37:295–299.

    CAS  PubMed  Google Scholar 

  140. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48:2741–2749.

    PubMed  Google Scholar 

  141. Kroot EJ, de Jong BA, van Leeuwen MA, et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2000;43:1831–1835.

    CAS  PubMed  Google Scholar 

  142. Lundberg K, Nijenhuis S, Vossenaar ER, et al. Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res Ther. 2005;7:R458–R467.

    CAS  PubMed  Google Scholar 

  143. Raza K, Breese M, Nightingale P, et al. Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis. J Rheumatol. 2005;32:231–238.

    CAS  PubMed  Google Scholar 

  144. n Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7:R949–R958.

    Google Scholar 

  145. Fusconi M, Vannini A, Dall’Aglio AC, et al. Anti-cyclic citrullinated peptide antibodies in type 1 autoimmune hepatitis. Aliment Pharmacol Ther. 2005;22:951–955.

    CAS  PubMed  Google Scholar 

  146. Montano-Loza A, Czaja AJ, Carpenter HA, et al. Frequency and significance of antibodies to cyclic citrullinated peptide in type 1 autoimmune hepatitis. Autoimmunity. 2006;39:341–348.

    CAS  PubMed  Google Scholar 

  147. Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ. PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays. 2003;25:1106–1118.

    CAS  PubMed  Google Scholar 

  148. Neubauer K, Knittel T, Armbrust T, Ramadori G. Accumulation and cellular localization of fibrinogen/fibrin during short-term and long-term rat liver injury. Gastroenterology. 1995;108:1124–1135.

    CAS  PubMed  Google Scholar 

  149. Czaja AJ. Autoimmune hepatitis. Part A: pathogenesis. Expert Rev Gastroenterol Hepatol. 2007;1:113–128.

    CAS  PubMed  Google Scholar 

  150. Strassburg CP, Kneip S, Topp J, et al. Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine. J Biol Chem. 2000;275:36164–36171.

    CAS  PubMed  Google Scholar 

  151. Izukawa T, Nakajima M, Fujiwara R, et al. Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers. Drug Metab Dispos. 2009;37:1759–1768.

    CAS  PubMed  Google Scholar 

  152. Ishii Y, Iwanaga M, Nishimura Y, et al. Protein–protein interactions between rat hepatic cytochromes P450 (P450 s) and UDP-glucuronosyltransferases (UGTs): evidence for the functionally active UGT in P450-UGT complex. Drug Metab Pharmacokinet. 2007;22:367–376.

    CAS  PubMed  Google Scholar 

  153. Obermayer-Straub P, Manns MP. Cytochrome P450 enzymes and UDP-glucuronosyltransferases as hepatocellular autoantigens. Mol Biol Rep. 1996;23:235–242.

    CAS  PubMed  Google Scholar 

  154. Manns MP, Obermayer-Straub P. Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease. Hepatology. 1997;26:1054–1066.

    CAS  PubMed  Google Scholar 

  155. Obermayer-Straub P, Strassburg CP, Manns MP. Target proteins in human autoimmunity: cytochromes P450 and UDP- glucuronosyltransferases. Can J Gastroenterol. 2000;14:429–439.

    CAS  PubMed  Google Scholar 

  156. Shinoda M, Tanaka Y, Kuno T, et al. High levels of autoantibodies against drug-metabolizing enzymes in SLA/LP-positive AIH-1 sera. Autoimmunity. 2004;37:473–480.

    CAS  PubMed  Google Scholar 

  157. Fabien N, Desbos A, Bienvenu J, Magdalou J. Autoantibodies directed against the UDP-glucuronosyltransferases in human autoimmune hepatitis. Autoimmun Rev. 2004;3:1–9.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  159. Neuberger J, Williams R. Immune mechanisms in tienilic acid associated hepatotoxicity. Gut. 1989;30:515–519.

    CAS  PubMed  Google Scholar 

  160. Lecoeur S, Andre C, Beaune PH. Tienilic acid-induced autoimmune hepatitis: anti-liver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol Pharmacol. 1996;50:326–333.

    CAS  PubMed  Google Scholar 

  161. Nishiya T, Mori K, Hattori C, et al. The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats. Toxicol Appl Pharmacol. 2008;232:280–291.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  163. Philipp T, Obermayer-Straub P, Manns MP. Autoantibodies in hepatitis delta. Biomed Pharmacother. 1995;49:344–349.

    CAS  PubMed  Google Scholar 

  164. Csepregi A, Nemesanszky E, Luettig B, Obermayer-Straub P, Manns MP. LKM3 autoantibodies in hepatitis C cirrhosis: a further phenomenon of the HCV-induced autoimmunity. Am J Gastroenterol. 2001;96:910–911.

    CAS  PubMed  Google Scholar 

  165. Dalekos GN, Makri E, Loges S, et al. Increased incidence of anti-LKM autoantibodies in a consecutive cohort of hepatitis C patients from central Greece. Eur J Gastroenterol Hepatol. 2002;14:35–42.

    CAS  PubMed  Google Scholar 

  166. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  168. 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.

    CAS  PubMed  Google Scholar 

  169. Invernizzi P, Selmi C, Ranftler C, Podda M, Wesierska-Gadek J. Antinuclear antibodies in primary biliary cirrhosis. Semin Liver Dis. 2005;25:298–310.

    PubMed  Google Scholar 

  170. Nakamura M, Kondo H, Mori T, et al. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology. 2007;45:118–127.

    CAS  PubMed  Google Scholar 

  171. Muratori P, Muratori L, Ferrari R, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol. 2003;98:431–437.

    PubMed  Google Scholar 

  172. Worman HJ, Courvalin JC. Antinuclear antibodies specific for primary biliary cirrhosis. Autoimmun Rev. 2003;2:211–217.

    PubMed  Google Scholar 

  173. 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.

    CAS  PubMed  Google Scholar 

  174. Courvalin JC, Worman HJ. Nuclear envelope protein autoantibodies in primary biliary cirrhosis. Semin Liver Dis. 1997;17:79–90.

    CAS  PubMed  Google Scholar 

  175. Milkiewicz P, Buwaneswaran H, Coltescu C, et al. Value of autoantibody analysis in the differential diagnosis of chronic cholestatic liver disease. Clin Gastroenterol Hepatol. 2009;7:1355–1360.

    PubMed  Google Scholar 

  176. Granito A, Yang WH, Muratori L, et al. PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis. Am J Gastroenterol. 2010;105:125–131.

    CAS  PubMed  Google Scholar 

  177. Worman HJ, Yuan J, Blobel G, Georgatos SD. A lamin B receptor in the nuclear envelope. Proc Natl Acad Sci USA. 1988;85:8531–8534.

    CAS  PubMed  Google Scholar 

  178. Courvalin JC, Lassoued K, Worman HJ, Blobel G. Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J Exp Med. 1990;172:961–967.

    CAS  PubMed  Google Scholar 

  179. Terjung B, Herzog V, Worman HJ, et al. Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins. Hepatology. 1998;28:332–340.

    CAS  PubMed  Google Scholar 

  180. Courvalin JC, Lassoued K, Bartnik E, Blobel G, Wozniak RW. The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. J Clin Invest. 1990;86:279–285.

    CAS  PubMed  Google Scholar 

  181. 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.

    CAS  PubMed  Google Scholar 

  182. Orth T, Gerken G, Meyer Zum Buschenfelde KH, Mayet WJ. Antineutrophil nuclear antibodies (ANNA) in primary biliary cirrhosis: their prevalence and antigen specificity. Z Gastroenterol. 1997;35:113–121.

    CAS  PubMed  Google Scholar 

  183. Szostecki C, Guldner HH, Netter HJ, Will H. Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J Immunol. 1990;145:4338–4347.

    CAS  PubMed  Google Scholar 

  184. 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.

    CAS  PubMed  Google Scholar 

  185. 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.

    CAS  PubMed  Google Scholar 

  186. 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.

    CAS  PubMed  Google Scholar 

  187. Muratori P, Muratori L, Cassani F, et al. Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders. Clin Exp Immunol. 2002;127:172–175.

    CAS  PubMed  Google Scholar 

  188. Czaja AJ, Muratori P, Muratori L, Carpenter HA, Bianchi FB. Diagnostic and therapeutic implications of bile duct injury in autoimmune hepatitis. Liver Int. 2004;24:322–329.

    PubMed  Google Scholar 

  189. Wichmann I, Montes-Cano MA, Respaldiza N, et al. Clinical significance of anti-multiple nuclear dots/Sp100 autoantibodies. Scand J Gastroenterol. 2003;38:996–999.

    CAS  PubMed  Google Scholar 

  190. Manuel Lucena J, Montes Cano M, Luis Caro J, et al. Comparison of two ELISA assays for anti-Sp100 determination. Ann NY Acad Sci. 2007;1109:203–211.

    PubMed  Google Scholar 

  191. Muratori P, Muratori L, Gershwin ME, et al. ‘True’ antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both? Clin Exp Immunol. 2004;135:154–158.

    CAS  PubMed  Google Scholar 

  192. Zuchner D, Sternsdorf T, Szostecki C, et al. Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatology. 1997;26:1123–1130.

    CAS  PubMed  Google Scholar 

  193. Shimoda S, Nakamura M, Ishibashi H, et al. Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology. 2003;124:1915–1925.

    CAS  PubMed  Google Scholar 

  194. Bogdanos DP, Baum H, Butler P, et al. Association between the primary biliary cirrhosis specific anti-sp100 antibodies and recurrent urinary tract infection. Dig Liver Dis. 2003;35:801–805.

    CAS  PubMed  Google Scholar 

  195. Worman HJ. Nuclear envelope protein autoantigens in primary biliary cirrhosis. Hepatol Res. 2007;37(Suppl 3):S406–S411.

    CAS  PubMed  Google Scholar 

  196. Nakamura M, Komori A, Ito M, et al. Predictive role of anti-gp210 and anticentromere antibodies in long-term outcome of primary biliary cirrhosis. Hepatol Res. 2007;37(Suppl 3):S412–S419.

    CAS  PubMed  Google Scholar 

  197. Gao L, Tian X, Liu B, Zhang F. The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med. 2008;8:9–15.

    CAS  PubMed  Google Scholar 

  198. Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC. The centromere: hub of chromosomal activities. Science. 1995;270:1591–1594.

    CAS  PubMed  Google Scholar 

  199. Bjerling P, Ekwall K. Centromere domain organization and histone modifications. Braz J Med Biol Res. 2002;35:499–507.

    CAS  PubMed  Google Scholar 

  200. Bernstein RM, Callender ME, Neuberger JM, Hughes GR, Williams R. Anticentromere antibody in primary biliary cirrhosis. Ann Rheum Dis. 1982;41:612–614.

    CAS  PubMed  Google Scholar 

  201. McHugh NJ, James IE, Fairburn K, Maddison PJ. Autoantibodies to mitochondrial and centromere antigens in primary biliary cirrhosis and systemic sclerosis. Clin Exp Immunol. 1990;81:244–249.

    Article  CAS  PubMed  Google Scholar 

  202. Hansen BU, Eriksson S, Lindgren S. High prevalence of autoimmune liver disease in patients with multiple nuclear dot, anti-centromere, and mitotic spindle antibodies. Scand J Gastroenterol. 1991;26:707–713.

    CAS  PubMed  Google Scholar 

  203. Chan HL, Lee YS, Hong HS, Kuo TT. Anticentromere antibodies (ACA): clinical distribution and disease specificity. Clin Exp Dermatol. 1994;19:298–302.

    CAS  PubMed  Google Scholar 

  204. Parveen S, Morshed SA, Nishioka M. High prevalence of antibodies to recombinant CENP-B in primary biliary cirrhosis: nuclear immunofluorescence patterns and ELISA reactivities. J Gastroenterol Hepatol. 1995;10:438–445.

    CAS  PubMed  Google Scholar 

  205. Granito A, Muratori P, Muratori L, et al. Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis. Aliment Pharmacol Ther. 2007;26:831–838.

    Article  CAS  PubMed  Google Scholar 

  206. Takada K, Suzuki K, Matsumoto M, et al. Primary biliary cirrhosis in female subjects with sicca-associated antibodies. Mod Rheumatol. 2007;17:486–491.

    PubMed  Google Scholar 

  207. Whyte J, Soriano E, Earnshaw WC, McHugh NJ. Frequency of autoantibodies to a major epitope on the carboxyl terminal fragment of CENP-B in patients with autoimmune disease. Br J Rheumatol. 1995;34:407–412.

    CAS  PubMed  Google Scholar 

  208. Miyawaki S, Asanuma H, Nishiyama S, Yoshinaga Y. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol. 2005;32:1488–1494.

    PubMed  Google Scholar 

  209. Stahnke G, Meier E, Scanarini M, Northemann W. Eukaryotic expression of recombinant human centromere autoantigen and its use in a novel ELISA for diagnosis of CREST syndrome. J Autoimmun. 1994;7:107–118.

    CAS  PubMed  Google Scholar 

  210. Himoto T, Nakai S, Kinekawa F, et al. Clinical characteristics of patients with hepatitis C virus-related chronic liver disease seropositive for anticentromere antibody. Dig Dis Sci. 2009;54:360–368.

    PubMed  Google Scholar 

  211. Parveen S, Morshed SA, Arima K, et al. Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA association. Dig Dis Sci. 1998;43:1322–1331.

    CAS  PubMed  Google Scholar 

  212. Yang WH, Yu JH, Nakajima A, et al. Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure? Clin Gastroenterol Hepatol. 2004;2:1116–1122.

    PubMed  Google Scholar 

  213. Assassi S, Fritzler MJ, Arnett FC, et al. Primary biliary cirrhosis (PBC), PBC autoantibodies, and hepatic parameter abnormalities in a large population of systemic sclerosis patients. J Rheumatol. 2009;36:2250–2256.

    PubMed  Google Scholar 

  214. Montano-Loza AJ, Carpenter HA, Czaja AJ. Frequency, behavior, and prognostic implications of antimitochondrial antibodies in type 1 autoimmune hepatitis. J Clin Gastroenterol. 2008;42:1047–1053.

    PubMed  Google Scholar 

  215. Vergani D, Alvarez F, Bianchi FB, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol. 2004;41:677–683.

    PubMed  Google Scholar 

  216. Bogdanos DP, Choudhuri K, Vergani D. Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences. Liver. 2001;21:225–232.

    CAS  PubMed  Google Scholar 

  217. Czaja AJ. Understanding the pathogenesis of autoimmune hepatitis. Am J Gastroenterol. 2001;96:1224–1231.

    CAS  PubMed  Google Scholar 

  218. Lapierre P, Beland K, Alvarez F. Pathogenesis of autoimmune hepatitis: from break of tolerance to immune-mediated hepatocyte apoptosis. Transl Res. 2007;149:107–113.

    CAS  PubMed  Google Scholar 

  219. Vergani D, Mieli-Vergani G. Aetiopathogenesis of autoimmune hepatitis. World J Gastroenterol. 2008;14:3306–3312.

    CAS  PubMed  Google Scholar 

  220. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2009;34:7–14.

    PubMed  Google Scholar 

  221. Herkel J, Lohse AW. Significance of autoantibodies. Hepatology. 2008;47:786–788.

    PubMed  Google Scholar 

  222. Czaja AJ. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2008;6:379–388.

    CAS  PubMed  Google Scholar 

  223. Muratori P, Czaja AJ, Muratori L, et al. Evidence of a genetic basis for the different geographic occurrences of liver/kidney microsomal antibody type 1 in hepatitis C. Dig Dis Sci. 2007;52:179–184.

    PubMed  Google Scholar 

  224. Szostecki C, Krippner H, Penner E, Bautz FA. Autoimmune sera recognize a 100-kD nuclear protein antigen (sp-100). Clin Exp Immunol. 1987;68:108–116.

    CAS  PubMed  Google Scholar 

  225. Czaja AJ. Emerging opportunities for site-specific molecular and cellular interventions in autoimmune hepatitis. Dig Dis Sci (in press).

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Czaja, A.J. Autoantibodies as Prognostic Markers in Autoimmune Liver Disease. Dig Dis Sci 55, 2144–2161 (2010). https://doi.org/10.1007/s10620-010-1268-4

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