Journal of Hepatology
Volume 41, Issue 4 , Pages 677-683 , October 2004

Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group

  • Diego Vergani

      Affiliations

    • Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44-20-7346-3305/3695; fax: +44-20-7346-3700.
    • ,
  • Fernando Alvarez

      Affiliations

    • Division of Gastroenterology, Hôpital Sainte-Justine, Montreal, Que., Canada, H3T IC5
    • ,
  • Francesco B. Bianchi

      Affiliations

    • Department of Internal Medicine, Cardioangiology, Hepatology, Policlinico S. Orsola University of Bologna, 40138 Bologna, Italy
    • ,
  • Eduardo L.R. Cançado

      Affiliations

    • Department of Gastroenterology, University of Sao Paulo School of Medicine, Brazil
    • ,
  • Ian R. Mackay

      Affiliations

    • Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia
    • ,
  • Michael P. Manns

      Affiliations

    • Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, 30625 Hannover, Germany
    • ,
  • Mikio Nishioka

      Affiliations

    • Ehime Rousai Hospital, Japan Labour Health and Welfare Organisation, 13-27 Minami-Komatsubara, Niihama, Ehime 792-0863, Japan
    • ,
  • Edward Penner

      Affiliations

    • Fourth Department of Internal Medicine, Vienna Medical University, Währinger Gürtel 18-20, A-1090 Vienna, Austria

References 

  1. Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology. 1993;18:998–1005
  2. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–938
  3. Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997;25:541–547
  4. Homberg JC, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil SH, et al. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of autoimmune hepatitis. Hepatology. 1987;7:1333–1339
  5. Taylor SL, Dean PJ, Riely CA. Primary autoimmune cholangitis. An alternative to antimitochondrial antibody-negative primary biliary cirrhosis. Am J Surg Pathol. 1994;18:91–99
  6. Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33:544–553
  7. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342:1266–1271
  8. Bonifacio E, Bingley PJ, Shattock M, Dean BM, Dunger D, Gale EA, et al. Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet. 1990;335:147–149
  9. Lernmark A, Molenaar JL, van Beers WA, Yamaguchi Y, Nagataki S, Ludvigsson J, et al. The Fourth International Serum Exchange Workshop to standardize cytoplasmic islet cell antibodies. The immunology and diabetes workshops and participating laboratories. Diabetologia. 1991;34:534–535
  10. Mire-Sluis AR, Das RG, Lernmark A. The development of a World Health Organisation international standard for islet cell antibodies: the aims and design of an international collaborative study. Diabetes Metab Res Rev. 1999;15:72–77
  11. Tan EM, Feltkamp TE, Smolen JS, Butcher B, Dawkins R, Fritzler MJ, et al. Range of antinuclear antibodies in healthy individuals. Arthritis Rheum. 1997;40:1601–1611
  12. 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
  13. Bottazzo GF, Florin-Christensen A, Fairfax A, Swana G, Doniach D, Groeschel-Stewart U. Classification of smooth muscle autoantibodies detected by immunofluorescence. J Clin Pathol. 1976;29:403–410
  14. Toh BH. Smooth muscle autoantibodies and autoantigens. Clin Exp Immunol. 1979;38:621–628
  15. Cancado EL, Abrantes-Lemos CP, Vilas-Boas LS, Novo NF, Carrilho FJ, Laudanna AA. Thermolabile and calcium-dependent serum factor interferes with polymerized actin, and impairs anti-actin antibody detection. J Autoimmun. 2001;17:223–228
  16. Muratori P, Muratori L, Agostinelli D, Pappas G, Veronesi L, Granito A, et al. Smooth muscle antibodies and type 1 autoimmune hepatitis. Autoimmunity. 2002;35:497–500
  17. 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
  18. Fritzler MJ, Manns MP. Anti-mitochondrial autoantibodies. Clin Appl Immunol Rev. 2002;3:87–113
  19. Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology. 1993;105:1522–1528
  20. Muratori P, Muratori L, Gershwin ME, Czaja AJ, Pappas G, MacCariello S, et al. True antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both?. Clin Exp Immunol. 2004;135:154–158
  21. Alvarez F, Bernard O, Homberg JC, Kreibich G. Anti-liver–kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum. J Exp Med. 1985;161:1231–1236
  22. Gueguen M, Meunier-Rotival M, Bernard O, Alvarez F. Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily. J Exp Med. 1988;168:801–806
  23. Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proc Natl Acad Sci USA. 1988;85:8256–8260
  24. Yamamoto AM, Johanet C, Duclos-Vallee JC, Bustarret FA, Alvarez F, Homberg JC, et al. A new approach to cytochrome CYP2D6 antibody detection in autoimmune hepatitis type-2 (AIH-2) and chronic hepatitis C virus (HCV) infection: a sensitive and quantitative radioligand assay. Clin Exp Immunol. 1997;108:396–400
  25. Ma Y, Gregorio G, Gaken J, Muratori L, Bianchi FB, Mieli-Vergani G, et al. Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection. J Hepatol. 1997;26:1396–1402
  26. Kerkar N, Ma Y, Davies ET, Cheeseman P, Mieli-Vergani G, Vergani D. Detection of liver kidney microsomal type 1 antibody using molecularly based immunoassays. J Clin Pathol. 2002;55:906–909
  27. Abuaf N, Johanet C, Chretien P, Martini E, Soulier E, Laperche S, et al. Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. Hepatology. 1992;16:892–898
  28. Lenzi M, Manotti P, Muratori L, Cataleta M, Ballardini G, Cassani F, et al. Liver cytosolic 1 antigen–antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. Gut. 1995;36:749–754
  29. 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
  30. Muratori L, Cataleta M, Muratori P, Manotti P, Lenzi M, Cassani F, 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
  31. 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
  32. Muratori L, Sztul E, Muratori P, Gao Y, Ripalti A, Ponti C, et al. Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1. Hepatology. 2001;34:494–501
  33. Bourdi M, Larrey D, Nataf J, Bernuau J, Pessayre D, Iwasaki M, et al. Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis. J Clin Invest. 1990;85:1967–1973
  34. Sacher M, Blumel P, Thaler H, Manns M. Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies. J Hepatol. 1990;10:364–369
  35. Clemente MG, Obermayer-Straub P, Meloni A, Strassburg CP, Arangino V, Tukey RH, et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1997;82:1353–1361
  36. Obermayer-Straub P, Perheentupa J, Braun S, Kayser A, Barut A, Loges S, et al. Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Gastroenterology. 2001;121:668–677
  37. Dalekos GN, Obermayer-Straub P, Bartels M, Maeda T, Kayser A, Braun S, et al. Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis C virus infection. J Hepatol. 2003;39:800–806
  38. Beaune P, Dansette PM, Mansuy D, Kiffel L, Finck M, Amar C, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sci USA. 1987;84:551–555
  39. Crivelli O, Lavarini C, Chiaberge E, Amoroso A, Farci P, Negro F, et al. Microsomal autoantibodies in chronic infection with the HBsAg associated delta (delta) agent. Clin Exp Immunol. 1983;54:232–238
  40. Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, et al. Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet. 1994;344:578–581
  41. Strassburg CP, Obermayer-Straub P, Alex B, Durazzo M, Rizzetto M, Tukey RH, et al. Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology. 1996;111:1576–1586
  42. 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
  43. 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
  44. Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver–pancreas antibodies in autoimmune hepatitis. Hepatology. 1993;18:1–9
  45. Wies I, Brunner S, Henninger J, Herkel J, Kanzler S, Meyer zum Buschenfelde KH, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet. 2000;355:1510–1515
  46. 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
  47. 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
  48. Volkmann M, Martin L, Baurle A, Heid H, Strassburg CP, Trautwein C, 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
  49. Baeres M, Herkel J, Czaja AJ, Wies I, Kanzler S, Cancado EL, et al. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut. 2002;51:259–264
  50. Ma Y, Okamoto M, Thomas MG, Bogdanos DP, Lopes AR, Portmann B, et al. Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology. 2002;35:658–664
  51. 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
  52. 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
  53. van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, et al. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985;1:425–429
  54. Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988;318:1651–1657
  55. Mulder AH, Horst G, Haagsma EB, Limburg PC, Kleibeuker JH, Kallenberg CG. Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology. 1993;17:411–417
  56. Targan SR, Landers C, Vidrich A, Czaja AJ. High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis. Gastroenterology. 1995;108:1159–1166
  57. Bansi DS, Fleming KA, Chapman RW. Antineutrophil cytoplasmic antibodies in autoimmune hepatitis. Gastroenterology. 1995;109:2049–2050
  58. Zauli D, Ghetti S, Grassi A, Descovich C, Cassani F, Ballardini G, et al. Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis. Hepatology. 1997;25:1105–1107
  59. Terjung B, Spengler U, Sauerbruch T, Worman HJ. Atypical p-ANCA in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology. 2000;119:310–322
  60. Terjung B, Worman HJ, Herzog V, Sauerbruch T, Spengler U. Differentiation of antineutrophil nuclear antibodies in inflammatory bowel and autoimmune liver diseases from antineutrophil cytoplasmic antibodies (p-ANCA) using immunofluorescence microscopy. Clin Exp Immunol. 2001;126:37–46

☆ The authors are the members of the committee for autoimmune serology of the International Autoimmune Hepatitis Group. DV is the chairman.

PII: S0168-8278(04)00367-8

doi: 10.1016/j.jhep.2004.08.002

Journal of Hepatology
Volume 41, Issue 4 , Pages 677-683 , October 2004

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