The Role of Liver Membrane Antigens as Targets in Autoimmune Type Liver Disease

  • K. H. Meyer zum Büschenfelde
  • T. H. Hütteroth
  • M. Manns
  • B. Möller


Autoimmune type chronic active hepatitis is clinically characterized by the presence of non-organ-specific autoantibodies, high gammaglobulin levels, circulating liver membrane autoantibodies, and the absence of hepatitis B virus markers. Host immune reactions against liver membrane antigens are regarded to be of significant importance for hepatic injury. Organ-specific determinants are of special interest whereas non-organ-specific determinants are believed to account for extrahepatic symptoms in chronic inflammatory liver diseases. In the present paper a review is given of the published data concerning the identification of liver membrane antigens. Furthermore the present knowledge of immune reactions against these target antigens will be reported and their clinical significance will be discussed.


Primary Biliary Cirrhosis Chronic Active Hepatitis Liver Membrane Chronic Active Liver Disease Inflammatory Liver Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arnold W, Hütteroth TH (to be published) Cellular immune reactions in non-B hepatitis. Basel Liver Week, MTP-Press, Lancaster, England, BaselGoogle Scholar
  2. 2.
    Bacon PA, Berry H, Bown R (1972) Cell-mediated immune reactivity in liver disease. Gut 13: 427PubMedCrossRefGoogle Scholar
  3. 3.
    Behrens UJ, Paronetto F (1979) Studies on.“liver-specific” antigens. I. Evaluation of the liver specificity of “LSP” and “LP-2”. Gastroenterology 77: 1045PubMedGoogle Scholar
  4. 4.
    Behrens UJ, Vernace S, Paronetto F (1979) Studies on “liver-specific” antigens. II. Detection of serum antibodies to liver and kidney cell membrane antigens in patients with chronic liver disease. Gastroenterology 77: 1053Google Scholar
  5. 5.
    Bolton A, Hunter W (1973) The labelling of proteins to high specific radioactivity by conjugation to a 125-I-containing acylating agent. Biochem J 133: 529PubMedGoogle Scholar
  6. 6.
    Butler RC (1978) Induction of chronic active hepatitis in rabbits immunized with purified human liver membrane lipoprotein. Workshop: Immune mechanisms in liver damage. 13th EASL Meeting, PaduaGoogle Scholar
  7. 7.
    Cochrane AMG, Moussouros A, Smith A, Portman B, Eddieston ALWF, Williams R (1978) Lymphocyte cytotoxicity in chronic active hepatitis: effect of therapy and correlations with clinical and histological changes. Gut 19: 308PubMedCrossRefGoogle Scholar
  8. 8.
    Facchini A, Stefanini GF, Bernardi M, Miglio G, Gasparini G, Labö G (1978) Lymphocytotoxicity test against rabbit hepatocytes in chronic liver diseases. Gut 19: 189PubMedCrossRefGoogle Scholar
  9. 9.
    Gerber MA, Lebwohl N, Thung SN, Bodenheimer H, Schaffner F (1979) Antibodies to liver-specific membrane protein in liver and kidney disease. (Abstract) Gastroenterology 76: 1281Google Scholar
  10. 10.
    Geubel AP, Keller RH, Summerskill WHJ, Dickson ER, Tomas TB, Shorter RG (1976) Lymphocyte cytotoxicity and inhibition studied with autologous liver cells: observations in chronic active liver disease and the primary biliary cirrhosis syndrome. Gastroenterology 71: 450PubMedGoogle Scholar
  11. 11.
    Hopf U, Meyer zum Büschenfelde KH (1974) Studies on the pathogenesis of the experimental chronic active hepatitis in rabbits. II. Demonstration of immunoglobulin on isolated hepatocytes. Br J Exp Pathol 55: 509Google Scholar
  12. 12.
    Hopf U, Meyer zum Büschenfelde KH, Arnold W (1975) Detection of a cytophilic autoantibody in chronic active hepatitis. (Letter) Lancet I: 690Google Scholar
  13. 13.
    Hopf U, Meyer zum Büschenfelde KH, Arnold W (1976) Detection of a liver membrane autoantibody in HBsAg-negative chronic active hepatitis. N Engl J Med 294: 578PubMedCrossRefGoogle Scholar
  14. 14.
    Hopf U, Meyer zum Büschenfelde KH, Hütteroth TH (1976) Humorale Immunreaktionen an der hepatocellulären Plasmamembran bei der experimentellen chronisch aktiven Hepatitis im Kaninchen. Klin Wochenschr 54: 591PubMedCrossRefGoogle Scholar
  15. 15.
    Hopf U, Meyer zum Büschenfelde KH, Freudenberg J (1974) Liver-specific antigens of different species. II. Localization of a membrane antigen at cell surface of isolated hepatocytes. Clin Exp Immunol 16: 117Google Scholar
  16. 16.
    Hütteroth TH, Arnold W, Meyer zum Büschenfelde KH (1980) Spontaneous (SCMC) and antibody mediated (ADCC) cellular cytotoxicity in chronic NANB hepatitis. International Symposium, Non- A, non-B hepatitis, Vienna 1980 (Abstract)Google Scholar
  17. 17.
    Hütteroth TH, Meyer zum Büschenfelde KH (1978) Clinical relevance of the liver-specific lipoprotein ( LSP ). Acta Hepatogastroenterol (Stuttg) 25: 243Google Scholar
  18. 18.
    Hütteroth TH, Meyer zum Büschenfelde KH (1978) Antigenic relationship between Chang liver cells and human hepatocytes. Klin Wochenschr 56: 525PubMedCrossRefGoogle Scholar
  19. 19.
    Hunter WM, Greenwood FC (1962) Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 193: 595Google Scholar
  20. 20.
    Jensen DM, McFarlane IG, Portmann BS, Eddieston DM, Williams R (1978) Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis. N Engl J Med 299: 1PubMedCrossRefGoogle Scholar
  21. 21.
    Junge U, Knaak G, Winckler K (1979) Untersuchungen zur Spezifität und Häufigkeit von Leberzell- Membran-Antikörpern. Z Gastroenterol (Abstract) 17: 649Google Scholar
  22. 22.
    Kakumu S, Arakawa Y, Goji H, Kashio T, Yata K (1979) Occurrence and significance of antibody to liver-specific membrane lipoprotein by double-antibody immunoprecipitation method in sera of patients with acute and chronic liver diseases. Gastroenterology 76: 665PubMedGoogle Scholar
  23. 23.
    Kakumu S, Hara T, Gohji H, Sakamoto N (1978) Inhibition of lymphocyte cytotoxicity in chronic active hepatitis. Clin Exp Immunol 33: 71PubMedGoogle Scholar
  24. 24.
    Kawanishi H (1977) In vitro studies on IgG mediated lymphocyte cytotoxicity in chronic active liver disease. Gastroenterology 73: 549PubMedGoogle Scholar
  25. 25.
    Kawanishi H, MacDermott RP (1979) K-cell-mediated antibody dependent cellular cytotoxicity in chronic active liver disease. Gastroenterology 76: 151PubMedGoogle Scholar
  26. 26.
    Kössling FK, Meyer zum Büschenfelde KH (1968) Zur Induktion einer aktiven chronischen Hepatitis durch heterologe lösliche Leberproteine. Virchows Arch [Pathol Anat] 345: 365CrossRefGoogle Scholar
  27. 27.
    Kössling FK, Meyer zum Büschenfelde KH (1970) Untersuchungen über die immunobiologische Bedeutung löslicher Leberproteine. Z Ges Exp Med 148: 131Google Scholar
  28. 28.
    Lee WM, Reed WD, Mitchell CG (1975) Cellular and humoral immunity to hepatitis B surface antigen in active chronic hepatitis. Br Med J I: 705Google Scholar
  29. 29.
    Manns M, Meyer zum Büschenfelde KH, Hütteroth TH, Hess G (to be published) Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid phase radioimmunoassay. Clin Exp ImmunolGoogle Scholar
  30. 30.
    Manns M, Meyer zum Büschenfelde KH, Hess G (to be published) Autoantibodies against liver specific protein: Studies on disease-, species- and organ-specificity. GutGoogle Scholar
  31. 31.
    Manns M, Meyer zum Büschenfelde KH, Hütteroth TH, Hopf U (1980) The liver specific protein: Evidence for species-specific and non-species-specific determinants. J Clin Lab Immunol 3: 9Google Scholar
  32. 32.
    McFarlane IG, Wojcicka BM, Zucker GM, Eddieston AL, WF (1977) Purification and characteri¬zation of human liver-specific membrane lipoprotein ( LSP ). Clin Exp Immunol 27: 381Google Scholar
  33. 33.
    Meyer zum Büschenfelde KH, Hopf U (1974) Studies on the pathogenesis of experimental chronic active hepatitis in rabbits. I. Induction of the disease and protective effect of allogeneic liver specific proteins. Br J Exp Pathol 55: 498Google Scholar
  34. 34.
    Meyer zum Büschenfelde KH, Kössling FK, Miescher PA (1972) Experimental chronic active hepatitis in rabbits following immunization with human liver proteins. Clin Exp Immunol 10: 99Google Scholar
  35. 35.
    Meyer zum Büschenfelde KH, Knolle J, Berger J (1974) Celluläre Immunreaktionen gegenüber homologen leberspezifischen Antigenen ( HLP) bei chronischen Leberentzündungen. Klin Wochenschr 52: 246Google Scholar
  36. 36.
    Meyer zum Büschenfelde KH, 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
  37. 37.
    Meyer zum Büschenfelde KH, Miescher PA (1972) Liver specific antigens. Purification and characterization. Clin Exp Immunol 10: 89Google Scholar
  38. 38.
    Meyer zum Büschenfelde KH, Alberti A, Arnold W, Freudenberg J (1975) Organ-specificity and diagnostic value of cell-mediated immunity against a liver-specific membrane protein: studies in hepatic and non-hepatic diseases. Klin Wochenschr 53: 1061PubMedCrossRefGoogle Scholar
  39. 39.
    Meyer zum Büschenfelde KH, Hütteroth TH, Arnold W, Hopf U (1979) Immunologic liver injury: The role of hepatitis B viral antigens and liver membrane antigens as targets. Prog Liver Dis 6: 407Google Scholar
  40. 40.
    Miller J, Smith MGM, Mitchell CG, Reed WD, Eddieston ALWG, Williams R (1972) Cell mediated immunity to a human liver-specific antigen in patients with active chronic hepatitis and primary biliary cirrhosis. Lancet II: 296Google Scholar
  41. 41.
    Paronetto F, Vernace S (1975) Immunological studies in patients with chronic active hepatitis. Cytotoxic activity of lymphocytes to autochthonous liver cells grown in tissue culture. Clin Exp Immunol 19: 99Google Scholar
  42. 42.
    Schuurman HJ, Vögten AJM, Schalm SW (1979) Specificity and sensitivity of the liver cell membrane autoantibody assay. 14th meeting of the European Association for the Study of the Liver. Düsseldorf, Sept. 13–15Google Scholar
  43. 43.
    Tage-Jensen U, Arnold W, Dietrichson O, Hardt F, Hopf U, Meyer zum Büschenfelde KH, Nielsen JO (1977) Liver-cell-membrane autoantibody specific for inflammatory liver diseases. Br Med J I: 206Google Scholar
  44. 44.
    Thestrup-Pedersen K, Ladefoged K, Andresen P (1976) Lymphocyte transformation test with liver- specific protein and phytohaemagglutinin in patients with liver disease. Clin Exp Immunol 24: 1PubMedGoogle Scholar
  45. 45.
    Thomson AD, Cochrane MAG, Mac-Farlane IG, Eddleston AL WF, Williams R (1974) Lymphocyte cytotoxicity to isolated hepatocytes in chronic active hepatitis. Nature 252: 721PubMedCrossRefGoogle Scholar
  46. 46.
    Tobias H, Safran AP, Schaffner F (1967) Lymphocyte stimulation and chronic liver disease. Lancet I: 193Google Scholar
  47. 47.
    Uibo R, Salaspuro M, Helin H, Krohn KJE (1980) Anti-LSP antibodies in man and in experimental hepatitis in rabbits. (Abstract) Hepato-Gastroenterology Supplement 302Google Scholar
  48. 48.
    Vergani GM, Vergani D, Jenkins PJ, Portman B, Mowat P, Eddleston ALWF, Williams R (1979) Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg-negative chronic active hepatitis. Clin Exp Immunol 38: 16PubMedGoogle Scholar
  49. 49.
    Vierling JM, Nelson DL, Strober W, Bundy BM, Jones EA (1977) In vitro cell mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis. J Clin Invest 60: 1116PubMedCrossRefGoogle Scholar
  50. 50.
    Vogten AJM, Hadzic H, Shorter RG, Summerskill WHJ, Taylor WF (1978) Cell-mediated cytotoxicity in chronic active liver disease: a new test system. Gastroenterology 74: 883PubMedGoogle Scholar
  51. 51.
    Wands JR, Isselbacher KJ (1975) Lymphocyte cytotoxicity to autologous liver cells in chronic active hepatitis. Proc Natl Acad Sci USA 72: 1301PubMedCrossRefGoogle Scholar
  52. 52.
    Wands JR, Perrotto L, Alpert E (1975) Cell mediated immunity in acute and chronic hepatitis. J Clin Invest 55: 921PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • K. H. Meyer zum Büschenfelde
    • 1
  • T. H. Hütteroth
    • 1
  • M. Manns
    • 1
  • B. Möller
    • 1
  1. 1.Abteilung für Innere Medizin und PoliklinikKlinikum Charlottenburg, Freie Universität BerlinBerlin 19Germany

Personalised recommendations