Genetic Determinants of Autoimmune Chronic Active Hepatitis

  • Ian R. Mackay
  • Senga Whittingham
  • John D. Mathews
  • Brian D. Tait


There has been a remarkable vindication over the past 15 years of Burnet’s forecast, with two particular themes of dominant interest to research on immunogenetics. The first is the association in inbred animals between genetic control of immune responses to antigens of limited heterogeneity and genes (Ir genes) of the major histocompatibility complex (MHC) [2, 39]. The second is the increasing refinement of typing methods for human histocompatibility antigens, of relevance to tissue transplantation, and associations between certain immunopathic diseases and HLA specificities [26, 31]. However, despite much experimental work and theoretical speculation, no unifying concept relating MHC-linked Ir genes effects and MHC- linked disease susceptibility has yet emerged.


Major Histocompatibility Complex Primary Biliary Cirrhosis Chronic Active Hepatitis Chronic Active Liver Disease Lupoid Hepatitis 
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  1. 1.
    Bach BA, Greene MI, Benacerraf B, Nisonoff A (1979) Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes. J Exp Med 149: 1084Google Scholar
  2. 2.
    Benacerraf B, Germain R (1978) The immune response genes of the major histocompatibility complex. Immunol Rev 38: 70PubMedCrossRefGoogle Scholar
  3. 3.
    Blomberg G, Geckeier WR, Weigert M (1972) Genetics of the antibody response to dextran in mice. Science 177: 178PubMedCrossRefGoogle Scholar
  4. 4.
    Burnet FM (1948) The basis of allergic disease. Med J Aust 1: 29PubMedGoogle Scholar
  5. 5.
    Coovadia HM, Mackay IR, d’Apice AJF (to be published) Suppressor cells assayed by three different methods in patients with chronic active hepatitis and systemic lupus erythematosus. Clin Immunol ImmunopathGoogle Scholar
  6. 6.
    De Groote J, Desmet VJ, Gedigk P, Korb G, Popper H, Poulsen H, Scheuer PJ, Schmid M, Thaler H, Uehlinger E, Wepler W (1968) A classification of chronic hepatitis. Lancet 2: 626PubMedCrossRefGoogle Scholar
  7. 7.
    Eddieston ALWF, Williams R (1978) HLA and liver disease. Br Med Bull 34: 295Google Scholar
  8. 8.
    Farid NR, Newton RM, Elke PN, Marshall WH (1977) Gm phenotypes in autoimmune disease. J Immunogenet 4: 429PubMedCrossRefGoogle Scholar
  9. 9.
    Freudenberg J, Baumann H, Arnold W, Berger J, Meyer zum Büschenfelde K-H (1977) HLA in different forms of chronic active hepatitis. A comparison between adult patients and children. Digestion 15: 260Google Scholar
  10. 10.
    Galbraith RM, Smith M, Mackenzie RM, Tee DE, Doniach D, Williams R (1974) High prevalence of sero-immunologic abnormalities in relatives of patients with active chronic hepatitis or primary biliary cirhosis. N Engl J Med 220: 63CrossRefGoogle Scholar
  11. 11.
    Geall MG, Schoenfield LJ, Summerskill WHJ (1968) Classification and treatment of chronic active liver disease. Gastroenterology 55: 724PubMedGoogle Scholar
  12. 12.
    Hill RN, Clemens TL, Liu D-K, Vesell ES, Johnson DN (1975) Genetic control of chloroform toxicity in mice. Science 190: 159PubMedCrossRefGoogle Scholar
  13. 13.
    Histocompatibility Testing 1977 (1978) Bodmer WF, Batchelor JR, Bodmer JG, Festenstein H, Morris PJ (eds) Munksgaard, CopenhagenGoogle Scholar
  14. 14.
    Hodgson HJF, Wands JR, Isselbacher KJ (1978) Alteration in suppressor cell activity in chronic active hepatitis. Proc Natl Acad Sci USA 75: 1549PubMedCrossRefGoogle Scholar
  15. 15.
    Hooper B, Whittingham S, Mathews JD, Mackay IR, Curnow DH (1972) Autoimmunity in a rural community. Clin Exp Immunol 12: 79PubMedGoogle Scholar
  16. 16.
    International Group (1977) Acute and chronic hepatitis revisited. Lancet 2: 914Google Scholar
  17. 17.
    Leevy CM, Popper H, Sherlock S (1976) Diseases of the liver and biliary tract. Standardization of nomenclature, diagnostic criteria and diagnostic methodology. Fogarty International Center Proceedings No. 22, DHEW Publication No. (NIH) 76–725. U.S. Government Printing Office, Washington DCGoogle Scholar
  18. 18.
    Mackay IR (1968) Lupoid hepatitis and primary biliary cirrhosis: autoimmune diseases of the liver? Bull Rheum Dis 18: 487Google Scholar
  19. 19.
    Mackay IR (1975) Chronic active hepatitides. Front Gastrointest Res 1: 142PubMedGoogle Scholar
  20. 20.
    Mackay IR (1977) HLA and liver disease. In: Dausset J, Svejgaard A (eds) HLA and disease. Munksgaard, Copenhagen, p 186Google Scholar
  21. 21.
    Mackay IR, Morris PJ (1972) Association of autoimmune active chronic hepatitis with HL-A1,8. Lancet 2: 793PubMedCrossRefGoogle Scholar
  22. 22.
    Mackay IR, Taft LI, Cowling DC (1956) Lupoid hepatitis. Lancet 2: 1323CrossRefGoogle Scholar
  23. 23.
    Mackay IR, Tait BD (1980) HLA associations with autoimmune-type chronic active hepatitis: identification of B8-DRw3 haplotype by family studies. Gastroenterology 79: 95PubMedGoogle Scholar
  24. 24.
    Mackay IR, Whittingham S, Tait B (1977) Genetic control of immune responsiveness in man. Vox Sang 32: 10PubMedCrossRefGoogle Scholar
  25. 25.
    Mazzilli MC, Trabace S, Di Raimondo F, Visco G, Gandini E (1977) HLA and chronic active hepatitis. Digestion 15: 278PubMedCrossRefGoogle Scholar
  26. 26.
    McDevitt HO, Bodmer WF (1974) HLA, immune response genes, and disease. Lancet 1: 1269PubMedCrossRefGoogle Scholar
  27. 27.
    McFarlane IG, Wojcicka BM, Williams R (1980) Antigens of the human liver. Clin Exp Immunol 40: 1PubMedGoogle Scholar
  28. 28.
    Meyer zum Büschenfelde K-H, Hütteroth TH (1979) Autoantibodies against liver membrane antigens in chronic active liver diseases. In Eddieston ALWF, Weber JCP, Williams R (eds) Immune reactions in liver disease. Pitman Medical, London, p 12Google Scholar
  29. 29.
    Meyer zum Büschenfelde K-H, Manns M, Hütteroth TH, Hopf U, Arnold W (1979) LM-Ag and LSP — two different target antigens involved in the immunopathogenesis of chronic active hepatitis? Clin Exp Immunol 37: 205PubMedGoogle Scholar
  30. 30.
    Miller KB, Schwartz RS (1979) Familial abnormalities of suppressor-cell function in systemic lupus erythematosus. N Engl J Med 301: 803PubMedCrossRefGoogle Scholar
  31. 31.
    Morris PJ (1974) Histocompatibility systems, immune response, and disease in man. Contemp Top Immunobiol 3: 141PubMedGoogle Scholar
  32. 32.
    Morris PJ, Vaughan H, Tait BD, Mackay IR (1977) Histocompatibility antigen (HLA): associations with immunopathic diseases and with response to microbial antigens. Aust N Z J Med 7: 616PubMedCrossRefGoogle Scholar
  33. 33.
    Nakao Y, Matsumoto H, Miyazaki T, Nishitani H, Ota K, Fujita T, Tsuji K (1980) Gm allotypes in myasthenia gravis. Lancet 1: 677PubMedGoogle Scholar
  34. 34.
    Opelz G, Vögten AJM, Summerskill WHJ, Schalm SW, Terasaki PI (1977) HLA determinants in chronic active liver disease: possible relation of HLA-Dw3 to prognosis. Tissue Antigens 9: 36PubMedCrossRefGoogle Scholar
  35. 35.
    Penner E, Grabner G, Dittrich H, Mayr WR (1977) HLA antigens in HBs antigen positive chronic active hepatitis. Tissue Antigens 10: 63PubMedCrossRefGoogle Scholar
  36. 36.
    Rose NR, Bacon LD, Sundick RS (1976) Genetic determinants of thyroiditis in the OS chicken. Transplant Rev 31: 264PubMedGoogle Scholar
  37. 37.
    Ryder LP, Andersen E, Svejgaard A (1978) An HLA map of Europe. Hum Hered 28: 171PubMedCrossRefGoogle Scholar
  38. 38.
    Salaspuro MP, Laitinen OL, Lehtola J, Makkonen H, Rasanen JA, Sipponen P (1976) Immunological parameters, viral antibodies, and biochemical and histological findings in relatives of patients with chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol 11: 313PubMedGoogle Scholar
  39. 39.
    Schreffler DC, Chella DS (1975) The H2 major histocompatibility complex and the I immune response region: genetic variation, function and organization. Adv Immunol 20: 125CrossRefGoogle Scholar
  40. 40.
    Svejgaard A, Christy M, Nerup J, Platz P, Ryder LP, Thomsen M (1978) HLA and autoimmune disease with special reference to the genetics of insulin-dependent diabetes. In: Rose NR, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease. Elsevier North Holland Inc, New York, p 101Google Scholar
  41. 41.
    Tait BD, Mackay IR, Kastelan A, Dausset J, Mayer S, Okochi K (to be published) Chronic liver disease including chronic active hepatitis. In: Terasaki PI (ed) Histocompatibility testing 1980.Google Scholar
  42. 42.
    Talal N, Roubinian JR (1978) Sex hormones and autoimmunity. In: Rose NR, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease, Elsevier North Holland Inc, New York, p 163Google Scholar
  43. 43.
    Vögten AJM, Shorter RG, Opelz G (1979) HLA and cell mediated immunity in HBsAg negative chronic active hepatitis. Gut 20: 523PubMedCrossRefGoogle Scholar
  44. 44.
    Whittingham S, Mathews JD, Schanfield MS, Matthews JV, Tait BD, Morris PJ, Mackay IR (1980) Interactive effect of Gm allotypes and HLA-B locus antigens on the human antibody response to a bacterial antigen. Clin Exp Immunol 40: 8PubMedGoogle Scholar
  45. 45.
    Whittingham S, Mathews JD, Schanfield MS, Tait BD, Mackay IR (to be published) Interaction of HLA and Gm in autoimmune chronic active hepatitis. Clin Exp ImmunolGoogle Scholar
  46. 46.
    Williams RM, Martin S, Falchuk KR, Trey C, Dubey DP, Cannady WG, Fitzpatrick D, Noreen H, Dupont B, Yunis EJ (1978) Increased frequency of HLA-DRw4 in chronic active hepatitis. Vox Sang 35: 366PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • Ian R. Mackay
    • 1
    • 4
  • Senga Whittingham
    • 1
    • 4
  • John D. Mathews
    • 2
    • 4
  • Brian D. Tait
    • 3
  1. 1.Clinical Research UnitWalter and Eliza Hall Institute of Medical Research and the Royal Melbourne HospitalUSA
  2. 2.Department of MedicineThe University of MelbourneUSA
  3. 3.The Tissue Typing LaboratoryRoyal Melbourne HospitalUSA
  4. 4.National Health and Medical Research CouncilAustralia

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