Digestive Diseases and Sciences

, Volume 55, Issue 8, pp 2144–2161

Autoantibodies as Prognostic Markers in Autoimmune Liver Disease



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.


Autoantibodies Autoimmune hepatitis Primary biliary cirrhosis 


  1. 1.
    Bogdanos DP, Mieli-Vergani G, Vergani D. Autoantibodies and their antigens in autoimmune hepatitis. Semin Liver Dis. 2009;29:241–253.PubMedGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 4.
    Toh BH. Smooth muscle autoantibodies and autoantigens. Clin Exp Immunol. 1979;38:621–628.PubMedGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 6.
    Czaja AJ. Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance. Liver Transpl. 2002;8:505–513.PubMedGoogle Scholar
  7. 7.
    Czaja AJ. Autoantibodies in autoimmune liver disease. Adv Clin Chem. 2005;40:127–164.PubMedGoogle Scholar
  8. 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).Google Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 11.
    Lindor KD, Gershwin ME, Poupon R, et al. AASLD practice guidelines. Primary biliary cirrhosis. Hepatology. 2009;50:291–308.PubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 21.
    Gregorio GV, Portmann B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997;25:541–547.PubMedGoogle Scholar
  22. 22.
    Czaja AJ. Behavior and significance of autoantibodies in type 1 autoimmune hepatitis. J Hepatol. 1999;30:394–401.PubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedGoogle Scholar
  29. 29.
    Czaja AJ. Autoantibodies. Baillieres Clin Gastroenterol. 1995;9:723–744.PubMedGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 36.
    Lacerda MA, Ludwig J, Dickson ER, Jorgensen RA, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995;90:247–249.PubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 39.
    Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology. 1993;18:1–9.PubMedGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 45.
    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
  46. 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.PubMedGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 48.
    Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology (in press).Google Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.PubMedGoogle Scholar
  52. 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.PubMedGoogle Scholar
  53. 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.PubMedGoogle Scholar
  54. 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.PubMedGoogle Scholar
  55. 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.PubMedGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 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.PubMedGoogle Scholar
  58. 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.PubMedGoogle Scholar
  59. 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.PubMedGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.PubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. 63.
    Muratori P, Muratori L, Agostinelli D, et al. Smooth muscle antibodies and type 1 autoimmune hepatitis. Autoimmunity. 2002;35:497–500.PubMedGoogle Scholar
  64. 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.PubMedGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. 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.PubMedGoogle Scholar
  67. 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.PubMedGoogle Scholar
  68. 68.
    Soares A, Cunha R, Rodrigues F, Ribeiro H. Smooth muscle autoantibodies with F-actin specificity. Autoimmun Rev. 2009;8:713–716.PubMedGoogle Scholar
  69. 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.PubMedGoogle Scholar
  70. 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.PubMedGoogle Scholar
  71. 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.PubMedGoogle Scholar
  72. 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.PubMedGoogle Scholar
  73. 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.PubMedGoogle Scholar
  74. 74.
    Toh BH, Taylor R, Pollock W. F-actin reactive smooth muscle antibody in subjects with normal liver function. Pathology. 2009;41:572–575.PubMedGoogle Scholar
  75. 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.PubMedGoogle Scholar
  76. 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.PubMedGoogle Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. 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.PubMedGoogle Scholar
  79. 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.PubMedGoogle Scholar
  80. 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.PubMedGoogle Scholar
  81. 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.PubMedGoogle Scholar
  82. 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.PubMedGoogle Scholar
  83. 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.PubMedGoogle Scholar
  84. 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.PubMedGoogle Scholar
  85. 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.PubMedCrossRefGoogle Scholar
  86. 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.PubMedGoogle Scholar
  87. 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.PubMedGoogle Scholar
  88. 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.PubMedGoogle Scholar
  89. 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.PubMedGoogle Scholar
  90. 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.PubMedGoogle Scholar
  91. 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.PubMedGoogle Scholar
  92. 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.PubMedGoogle Scholar
  93. 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.PubMedGoogle Scholar
  94. 94.
    Czaja AJ, Shums Z, Norman GL. Nonstandard antibodies as prognostic markers in autoimmune hepatitis. Autoimmunity. 2004;37:195–201.PubMedGoogle Scholar
  95. 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.PubMedGoogle Scholar
  96. 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.PubMedGoogle Scholar
  97. 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.PubMedGoogle Scholar
  98. 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.PubMedGoogle Scholar
  99. 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.PubMedGoogle Scholar
  100. 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.PubMedGoogle Scholar
  101. 101.
    Mizuno M, Brown WR, Vierling JM. Ultrastructural immunocytochemical localization of the asialoglycoprotein receptor in rat hepatocytes. Gastroenterology. 1984;87:763–769.PubMedGoogle Scholar
  102. 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.PubMedGoogle Scholar
  103. 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.PubMedGoogle Scholar
  104. 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.PubMedGoogle Scholar
  105. 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.PubMedGoogle Scholar
  106. 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.PubMedGoogle Scholar
  107. 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.PubMedGoogle Scholar
  108. 108.
    Treichel U, McFarlane BM, Seki T, et al. Demographics of anti-asialoglycoprotein receptor autoantibodies in autoimmune hepatitis. Gastroenterology. 1994;107:799–804.PubMedGoogle Scholar
  109. 109.
    Husa P, Chalupa P, Stroblova H, et al. Autoantibodies to asialoglycoprotein receptor in chronic hepatitis C patients. Acta Virol. 2001;45:7–11.PubMedGoogle Scholar
  110. 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.PubMedGoogle Scholar
  111. 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.PubMedGoogle Scholar
  112. 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.PubMedGoogle Scholar
  113. 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.PubMedGoogle Scholar
  114. 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.PubMedCrossRefGoogle Scholar
  115. 115.
    Kakegawa T, Ise H, Sugihara N, et al. Soluble asialoglycoprotein receptors reflect the apoptosis of hepatocytes. Cell Transplant. 2002;11:407–415.PubMedGoogle Scholar
  116. 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.PubMedGoogle Scholar
  117. 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.PubMedGoogle Scholar
  118. 118.
    Diao J, Michalak TI. Virus-induced anti-asialoglycoprotein receptor autoimmunity in experimental hepadnaviral hepatitis. Hepatology. 1997;25:689–696.PubMedGoogle Scholar
  119. 119.
    Inamoto T, Brown WR. IgG is associated with the asialoglycoprotein receptor in the human liver. Hepatology. 1991;14:1070–1075.PubMedGoogle Scholar
  120. 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.PubMedGoogle Scholar
  121. 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.PubMedGoogle Scholar
  122. 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.PubMedGoogle Scholar
  123. 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.PubMedGoogle Scholar
  124. 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.PubMedGoogle Scholar
  125. 125.
    Doenecke D, Albig W, Bode C, et al. Histones: genetic diversity and tissue-specific gene expression. Histochem Cell Biol. 1997;107:1–10.PubMedGoogle Scholar
  126. 126.
    Burlingame RW, Cervera R. Anti-chromatin (anti-nucleosome) autoantibodies. Autoimmun Rev. 2002;1:321–328.PubMedGoogle Scholar
  127. 127.
    Amoura Z, Koutouzov S, Piette JC. The role of nucleosomes in lupus. Curr Opin Rheumatol. 2000;12:369–373.PubMedGoogle Scholar
  128. 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.PubMedGoogle Scholar
  129. 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.PubMedGoogle Scholar
  130. 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.PubMedGoogle Scholar
  131. 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.PubMedGoogle Scholar
  132. 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.PubMedGoogle Scholar
  133. 133.
    Penner E. Nature of immune complexes in autoimmune chronic active hepatitis. Gastroenterology. 1987;92:304–308.PubMedGoogle Scholar
  134. 134.
    Konikoff F, Swissa M, Shoenfeld Y. Autoantibodies to histones and their subfractions in chronic liver diseases. Clin Immunol Immunopathol. 1989;51:77–82.PubMedGoogle Scholar
  135. 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.PubMedGoogle Scholar
  136. 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.PubMedGoogle Scholar
  137. 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.PubMedGoogle Scholar
  138. 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.PubMedGoogle Scholar
  139. 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.PubMedGoogle Scholar
  140. 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.PubMedGoogle Scholar
  141. 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.PubMedGoogle Scholar
  142. 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.PubMedGoogle Scholar
  143. 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.PubMedGoogle Scholar
  144. 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. 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.PubMedGoogle Scholar
  146. 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.PubMedGoogle Scholar
  147. 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.PubMedGoogle Scholar
  148. 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.PubMedGoogle Scholar
  149. 149.
    Czaja AJ. Autoimmune hepatitis. Part A: pathogenesis. Expert Rev Gastroenterol Hepatol. 2007;1:113–128.PubMedGoogle Scholar
  150. 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.PubMedGoogle Scholar
  151. 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.PubMedGoogle Scholar
  152. 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.PubMedGoogle Scholar
  153. 153.
    Obermayer-Straub P, Manns MP. Cytochrome P450 enzymes and UDP-glucuronosyltransferases as hepatocellular autoantigens. Mol Biol Rep. 1996;23:235–242.PubMedGoogle Scholar
  154. 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.PubMedGoogle Scholar
  155. 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.PubMedGoogle Scholar
  156. 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.PubMedGoogle Scholar
  157. 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.PubMedGoogle Scholar
  158. 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.PubMedGoogle Scholar
  159. 159.
    Neuberger J, Williams R. Immune mechanisms in tienilic acid associated hepatotoxicity. Gut. 1989;30:515–519.PubMedGoogle Scholar
  160. 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.PubMedGoogle Scholar
  161. 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.PubMedGoogle Scholar
  162. 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.PubMedGoogle Scholar
  163. 163.
    Philipp T, Obermayer-Straub P, Manns MP. Autoantibodies in hepatitis delta. Biomed Pharmacother. 1995;49:344–349.PubMedGoogle Scholar
  164. 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.PubMedGoogle Scholar
  165. 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.PubMedGoogle Scholar
  166. 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.PubMedGoogle Scholar
  167. 167.
    Philipp T, Straub P, Durazzo M, Tukey RH, Manns MP. Molecular analysis of autoantigens in hepatitis D. J Hepatol. 1995;22:132–135.PubMedGoogle Scholar
  168. 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.PubMedGoogle Scholar
  169. 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.PubMedGoogle Scholar
  170. 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.PubMedGoogle Scholar
  171. 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.PubMedGoogle Scholar
  172. 172.
    Worman HJ, Courvalin JC. Antinuclear antibodies specific for primary biliary cirrhosis. Autoimmun Rev. 2003;2:211–217.PubMedGoogle Scholar
  173. 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.PubMedGoogle Scholar
  174. 174.
    Courvalin JC, Worman HJ. Nuclear envelope protein autoantibodies in primary biliary cirrhosis. Semin Liver Dis. 1997;17:79–90.PubMedGoogle Scholar
  175. 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.PubMedGoogle Scholar
  176. 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.PubMedGoogle Scholar
  177. 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.PubMedGoogle Scholar
  178. 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.PubMedGoogle Scholar
  179. 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.PubMedGoogle Scholar
  180. 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.PubMedGoogle Scholar
  181. 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.PubMedGoogle Scholar
  182. 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.PubMedGoogle Scholar
  183. 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.PubMedGoogle Scholar
  184. 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.PubMedGoogle Scholar
  185. 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.PubMedGoogle Scholar
  186. 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.PubMedGoogle Scholar
  187. 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.PubMedGoogle Scholar
  188. 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.PubMedGoogle Scholar
  189. 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.PubMedGoogle Scholar
  190. 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.PubMedGoogle Scholar
  191. 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.PubMedGoogle Scholar
  192. 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.PubMedGoogle Scholar
  193. 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.PubMedGoogle Scholar
  194. 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.PubMedGoogle Scholar
  195. 195.
    Worman HJ. Nuclear envelope protein autoantigens in primary biliary cirrhosis. Hepatol Res. 2007;37(Suppl 3):S406–S411.PubMedGoogle Scholar
  196. 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.PubMedGoogle Scholar
  197. 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.PubMedGoogle Scholar
  198. 198.
    Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC. The centromere: hub of chromosomal activities. Science. 1995;270:1591–1594.PubMedGoogle Scholar
  199. 199.
    Bjerling P, Ekwall K. Centromere domain organization and histone modifications. Braz J Med Biol Res. 2002;35:499–507.PubMedGoogle Scholar
  200. 200.
    Bernstein RM, Callender ME, Neuberger JM, Hughes GR, Williams R. Anticentromere antibody in primary biliary cirrhosis. Ann Rheum Dis. 1982;41:612–614.PubMedGoogle Scholar
  201. 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.PubMedCrossRefGoogle Scholar
  202. 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.PubMedGoogle Scholar
  203. 203.
    Chan HL, Lee YS, Hong HS, Kuo TT. Anticentromere antibodies (ACA): clinical distribution and disease specificity. Clin Exp Dermatol. 1994;19:298–302.PubMedGoogle Scholar
  204. 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.PubMedGoogle Scholar
  205. 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.PubMedCrossRefGoogle Scholar
  206. 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.PubMedGoogle Scholar
  207. 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.PubMedGoogle Scholar
  208. 208.
    Miyawaki S, Asanuma H, Nishiyama S, Yoshinaga Y. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol. 2005;32:1488–1494.PubMedGoogle Scholar
  209. 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.PubMedGoogle Scholar
  210. 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.PubMedGoogle Scholar
  211. 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.PubMedGoogle Scholar
  212. 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.PubMedGoogle Scholar
  213. 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.PubMedGoogle Scholar
  214. 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.PubMedGoogle Scholar
  215. 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.PubMedGoogle Scholar
  216. 216.
    Bogdanos DP, Choudhuri K, Vergani D. Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences. Liver. 2001;21:225–232.PubMedGoogle Scholar
  217. 217.
    Czaja AJ. Understanding the pathogenesis of autoimmune hepatitis. Am J Gastroenterol. 2001;96:1224–1231.PubMedGoogle Scholar
  218. 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.PubMedGoogle Scholar
  219. 219.
    Vergani D, Mieli-Vergani G. Aetiopathogenesis of autoimmune hepatitis. World J Gastroenterol. 2008;14:3306–3312.PubMedGoogle Scholar
  220. 220.
    Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2009;34:7–14.PubMedGoogle Scholar
  221. 221.
    Herkel J, Lohse AW. Significance of autoantibodies. Hepatology. 2008;47:786–788.PubMedGoogle Scholar
  222. 222.
    Czaja AJ. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2008;6:379–388.PubMedGoogle Scholar
  223. 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.PubMedGoogle Scholar
  224. 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.PubMedGoogle Scholar
  225. 225.
    Czaja AJ. Emerging opportunities for site-specific molecular and cellular interventions in autoimmune hepatitis. Dig Dis Sci (in press).Google Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyMayo Clinic College of MedicineRochesterUSA

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