Skip to main content
SpringerLink
Log in

Immunological Injury to the Intestine and Liver in Human Marrow Transplant Recipients

  • Chapter
Modern Concepts in Gastroenterology Volume 2

Part of the book series: Topics in Gastroenterology ((TGEN))

  • 59 Accesses

Abstract

Over 3000 marrow transplants are now carried out yearly, a number that will surely increase as long-term survival after marrow grafting improves. Patients are returning to their community physicians having been “cured” of their original diseases but suffering the sequelae of the marrow transplant procedure. On another plane, it is of great interest that marrow Transplantation creates intestinal and liver diseases that are similar to several puzzling, naturally occurring human illnesses. For example, acute graft-versus-host disease (GVHD) causes a form of inflammatory bowel disease that is most prominent in the ileocecal region. Chronic graft-versus-host disease in the liver looks much like primary biliary cirrhosis, and in the esophagus, like epidermolysis bullosa. This chapter will summarize the clinical presentation and pathophysiology of intestinal and liver injury after Transplantation, especially that mediated by the immune system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Storb R, Thomas ED. Allogeneic bone marrow Transplantation. Immunol Rev 1983;71:77–102.

    Article  PubMed  CAS  Google Scholar 

  2. Storb R, Thomas ED, Buckner CD et al. Marrow Transplantation for aplastic anemia. Semin Hematol 1984;21:27–35.

    PubMed  CAS  Google Scholar 

  3. O’Reilly RJ, Brochstein J, Dinsmore R, Kirkpatrick D. Marrow Transplantation for congenital disorders. Semin Hematol 1984;21:188–221.

    PubMed  Google Scholar 

  4. Martin PJ, Hansen JA, Storb R, Thomas ED. Human marrow Transplantation: an immunological perspective. Adv Immunol 1987;40:379–438.

    Article  PubMed  CAS  Google Scholar 

  5. Parkman R. The application of bone marrow Transplantation to the treatment of genetic diseases. Science 1986;232:1373–1378.

    Article  PubMed  CAS  Google Scholar 

  6. McDonald GB, Shulman HM, Sullivan KM, Spencer GD. Intestinal and hepatic complications of human bone marrow Transplantations. Gastroenterology 1986;90:460–477, 770–784.

    PubMed  Google Scholar 

  7. McDonald GB, Shulman HM, Wolford JL, Spencer GD. Liver disease after human marrow Transplantation. Semin Liver Dis 1987;7:210–229.

    Article  PubMed  CAS  Google Scholar 

  8. Ferrara JLM. Syngeneic graft-vs-host disease. Arch Dermatol 1987;123:741–742.

    Article  PubMed  CAS  Google Scholar 

  9. Deeg HJ, Storb R. Acute and chronic graft-versus-host disease: clinical manifestations, prophylaxis, and treatment. J Natl Cancer Inst 1986;76:1325–1328.

    PubMed  CAS  Google Scholar 

  10. Neudorf S, Filipovich A, Ramsay NKC, Kersey J. Prevention and treatment of acute graft-versus-host disease. Semin Hematol 1984;21:91–100.

    PubMed  CAS  Google Scholar 

  11. Storb R, Deeg HJ, Whitehead J et al. Marrow Transplantation for leukemia: A controlled trial of a combination of methotrexate and cyclosporine versus cyclosporin alone for prophylaxis of acute graft-versus-host disease. N Engl J Med 1986;314:729–735.

    Article  PubMed  CAS  Google Scholar 

  12. Storb R, Deeg HJ, Farewell V et al. Marrow Transplantation for severe aplastic anemia: Methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease. Blood 1986;68:119–125.

    PubMed  CAS  Google Scholar 

  13. Sullivan KM, Deeg HJ, Sanders J et al. Hyperacute graft-versus-host disease in patients not given immunosuppression after allogeneic marrow Transplantation. Blood 1986;67:1172–1175.

    PubMed  CAS  Google Scholar 

  14. Witherspoon RP, Lum LG, Storb R. Immunologic reconstitution after human marrow grafting. Semin Hematol 1984;21:2–10.

    PubMed  CAS  Google Scholar 

  15. Atkinson K, Farewell V, Storb R et al. Analysis of late infections after human bone marrow Transplantation. Role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood 1982;60:714–720.

    PubMed  CAS  Google Scholar 

  16. Sullivan KM. Graft-versus-host disease. In: Clinical Bone Marrow Transplantation (Blume KG, Petz LD, eds). New York: Churchill Livingstone, 1983, pp. 91–129.

    Google Scholar 

  17. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974;18:295–304.

    Article  PubMed  CAS  Google Scholar 

  18. Weiden PL, The Seattle Marrow Transplant Team. Graft-versus-host disease in allogeneic marrow Transplantation. In: Biology of Bone Marrow Transplantation (Gale RP, Fox DF, eds). New York: Academic Press, 1980, pp. 37–48.

    Google Scholar 

  19. Sullivan KM. Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 1986;4:42–93.

    Article  PubMed  Google Scholar 

  20. Weisdorf SA, Salati LM, Longsdorf JA et al. Graft-versus-host disease of the intestine: A protein losing enteropathy characterized by fecal alpha1-antitrypsin. Gastroenterology 1983;85:1076–1081.

    PubMed  CAS  Google Scholar 

  21. Spencer GD, Hackman RC, McDonald GB et al. A prospective study of unexplained nausea and vomiting after marrow Transplantation. Transplantation 1986;42:602–607.

    Article  PubMed  CAS  Google Scholar 

  22. Fisk JD, Shulman HM, Greening RR, McDonald GB, Sale GE, Thomas ED. Gastrointestinal radiographic features of human graft-versus-host disease. Am J Roentgenol 1981;136:329–336.

    CAS  Google Scholar 

  23. Maile CW, Frick MP, Crass JR et al. The plain abdominal radiograph in acute intestinal graft-versus-host disease. Am J Roentgenol 1985;145:289–292.

    CAS  Google Scholar 

  24. Spencer GD, Shulman HM, Myerson D, Thomas ED, McDonald GB. Diffuse intestinal ulceration after marrow Transplantation: A clinical-pathological study of 13 patients. Hum Pathol 1986;17:621–633.

    Article  PubMed  CAS  Google Scholar 

  25. Epstein RJ, McDonald GB, Sale GE, Shulman HM, Thomas ED. The diagnostic accuracy of the rectal biopsy in acute graft-versus-host disease: A prospective study of thirteen patients. Gastroenterology 1980;78:764–771.

    PubMed  CAS  Google Scholar 

  26. Snover DC, Weisdorf SA, Vercellotti GM et al. A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow Transplantation. Hum Pathol 1985;16:387–392.

    Article  PubMed  CAS  Google Scholar 

  27. McDonald GB, Sale GE. The human gastrointestinal tract after allogeneic marrow Transplantation. In: The Pathology of Bone Marrow Transplantation (Sale GE, Shulman HM, eds). New York: Masson, 1984, pp. 77–103.

    Google Scholar 

  28. Gallucci BB, Sale GE, McDonald GB, Epstein R, Shulman HM, Thomas ED. The fine structure of human rectal epithelium in acute graft-versus-host disease. Am J Surg Pathol 1982;6:293–305.

    Article  PubMed  CAS  Google Scholar 

  29. Podack ER. The molecular mechanism of lymphocyte-mediated tumor cell lysis. Immunol Today 1985;6:21–27.

    Article  CAS  Google Scholar 

  30. Otto HF. The interepithelial lymphocytes of the intestine. Morphological observations and immunological aspects of intestinal enteropathy. In: Current Topics of Pathology, Vol 57 (Altmann KW et al, eds). Berlin: Springer-Verlag, 1973, pp. 81–121.

    Google Scholar 

  31. Kotler DP,Gaetz HP, Lange M, Klein EB, Holt PR. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 1984;101:421–428.

    PubMed  CAS  Google Scholar 

  32. Snover DC, Filipovich AH, Ramsay NKC, Weisdorf SA, Kersey JH. Graft-versus-host disease-like histopathological findings in pre-bone-marrow Transplantation biopsies of patients with severe T cell deficiency. Transplantation 1985;39:95–97.

    Article  PubMed  CAS  Google Scholar 

  33. Snover DC. Mucosal damage simulating acute graft-versus-host-reaction in cytomegalovirus colitis. Transplantation 1984;39:669–670.

    Google Scholar 

  34. Duly SA, Sloane JP. Changes in rectal leucocytes after allogeneic bone marrow Transplantation. Clin Exp Immunol 1987;67:151–158.

    Google Scholar 

  35. Beschorner WE, Yardley JH, Tutschka P, Santos G. Deficiency of intestinal immunity with graft-versus-host disease in humans. J Infect Dis 1981;144:38–46.

    Article  PubMed  CAS  Google Scholar 

  36. Kolb H, Sale GE, Lerner KG, Storb R, Thomas ED. Pathology of acute graft-versus-host disease in the dog. An autopsy study of ninety-five dogs. Am J Pathol 1979;96:581–594.

    PubMed  CAS  Google Scholar 

  37. Weisdorf SA, Platt JL, Snover DC, Kersey JH, Scharp HL. In situ analysis of T and killer lymphocyte subpopulations in rectal biopsies from bone marrow transplant patients. Gastroenterology 1983;84:1348 (abstract).

    Google Scholar 

  38. Filipovich AH, McGlave PB, Ramsay NKC et al. Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone-marrow Transplantation. Lancet 1982;1:1266–1269.

    Article  PubMed  CAS  Google Scholar 

  39. Prentice HG, Blacklock HA, Janossy G et al. Use of anti-T-cell monoclonal antibody OKT3 to prevent acute graft-versus-host disease in allogeneic bone-marrow Transplantation for acute leukaemia. Lancet 1982;1:700–703.

    Article  PubMed  CAS  Google Scholar 

  40. Grebe SC, Streilein JW. Graft-versus-host reactions: A review. Adv Immunol 1976;22:119–221.

    Article  PubMed  CAS  Google Scholar 

  41. Elson CO, Reilly RW, Rosenberg IH. Small intestinal injury in the graft-versus-host reaction: An innocent bystander phenomenon. Gastroenterology 1977;72:886–889.

    PubMed  CAS  Google Scholar 

  42. Gallucci BB, Shulman HM, Sale GE, Lerner KG, Caldwell LE, Thomas ED. The ultrastructure of the human epidermis in chronic graft-versus-host disease. AM J Pathol 1979;95:643–662.

    PubMed  CAS  Google Scholar 

  43. van Bekkum DW, Knaan S. Role of bacterial microflora in development of intestinal lesions from graft-versus-host reaction. J Natl Cancer Inst 1977;58:787–790.

    PubMed  Google Scholar 

  44. Pollard M, Chang CF, Strivastava KK. The role of microflora in development of graft-versus-host disease. Trans Proc 1976;4:533–536.

    Google Scholar 

  45. Mee AS, McLaughlin JE, Hodgson HJF, Jewell DP. Chronic immune colitis in rabbits. Gut 1790;20:1–5.

    Google Scholar 

  46. Storb R, Prentice RL, Buckner CD et al. Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protected environment. N Engl J Med 1983;308:302–307.

    Article  PubMed  CAS  Google Scholar 

  47. Farthing MJG, Clark ML, Sloane JP et al. Liver disease after bone marrow Transplantation. Gut 1982;23:465–474.

    Article  PubMed  CAS  Google Scholar 

  48. Shulman HM, McDonald GB. Liver disease after marrow Transplantation. In: The Pathology of Bone Marrow Transplantation (Sale GE, Shulman HM, eds). New York: Masson, 1984, pp. 104–135.

    Google Scholar 

  49. Snover DC, Weisdorf SA, Ramsay NK et al. Hepatic graft-versus-host disease: A study of the predictive value of liver biopsy in diagnosis. Hepatology 1984;4:123–130.

    Article  PubMed  CAS  Google Scholar 

  50. Shulman HM, Sharma P, Amos D et al. A coded histologic study of hepatic graft-versus-host disease after human bone marrow Transplantation. Hepatology 1988;8:463–470.

    Article  PubMed  CAS  Google Scholar 

  51. Tanaka M, Umihara J, Chiba S, Ishikawa E. Intrahepatic bile duct injury following bone marrow Transplantation. Analysis of pathological features based on three-dimensional and his-tochemical observation. Acta Pathol J 1986;36:1793–1806.

    CAS  Google Scholar 

  52. Sloane JP, Farthing MJ, Powles RL. Histopathological changes in the liver after allogeneic bone marrow Transplantation. J Clin Pathol 1980;33:344–350.

    Article  PubMed  CAS  Google Scholar 

  53. Dilly SA, Sloane JP. An immunohistological study of human hepatic graft-versus-host disease. Clin Exp Immunol 1985;62:545–553.

    PubMed  CAS  Google Scholar 

  54. Bernuau D, Gisselbrecht C, Devergie A et al. Histological and ultrastructural appearance of the liver graft-versus-host disease complicating bone marrow Transplantation. Transplantation 1980;29:236–244.

    Article  PubMed  CAS  Google Scholar 

  55. Searle J, Kerr JFR, Battersby C et al. An electron microscopic study of the mode of donor cell death in unmodified rejection of pig liver allografts. Aust J Exp Biol Med Sci 1977;55:401–406.

    Article  PubMed  CAS  Google Scholar 

  56. Shearer GM, Levy RB. Graft-versus-host-associated immune suppression is activated by recognition of allogeneic murine I-A antigens. J Exp Med 1983;157:936–946.

    Article  PubMed  CAS  Google Scholar 

  57. Suitters AJ, Lampert IA. Class II antigen induction in the liver of rats with graft-versus-host disease. Transplantation 1984;38:194–196.

    Article  PubMed  CAS  Google Scholar 

  58. Takacs L, Szende B, Rot AS et al. Expression of MHC Class II antigens on bile duct epithelium in experimental graft-versus-host disease. Clin Exp Immunol 1985;60:449–456.

    PubMed  CAS  Google Scholar 

  59. Szetein MB, Steeg PS, Johnson HM, Oppenheim JJ. Regulation of human peripheral blood monocyte DR antigen expression in vitro by lymphokines and recombinant interferons. J Clin Invest 1984;73:556–565.

    Article  Google Scholar 

  60. Walker EB, Maino V, Sanchez-Lanier M et al. Murine gamma interferon activates the release of a macrophage-derived Ia-inducing factor that transfers la inductive capacity. J Exp Med 1984;159:1532–1547.

    Article  PubMed  CAS  Google Scholar 

  61. Lautenschlager I, Taskinen E, Inkinen K et al. Distribution of the major histocompatibility complex antigens on different cellular components of human liver. Cell Immunol 1984;85:191–200.

    Article  PubMed  CAS  Google Scholar 

  62. Ballardini G, Bianchi FB, Doniach D et al. Aberrant expression of HLA-DR antigens on bile duct epithelium in primary biliary cirrhosis: Relevance to pathogenesis. Lancet 1984;2:1009–1113.

    Article  PubMed  CAS  Google Scholar 

  63. Takacs L, Szende B, Monostori E et al. Expression of HLA-DR antigens on bile duct cells of rejected liver transplant. Lancet 1983;2:1500 (letter).

    Article  PubMed  CAS  Google Scholar 

  64. McDonald GB, Jewell DP. Class II antigen (HLA-DR) expression by intestinal epithelial cells in inflammatory disease of the colon. J Clin Pathol 1984;40:312–317.

    Article  Google Scholar 

  65. Sullivan KM, Shulman HM, Storb R et al. Chronic graft-versus-host disease in 52 patients: Adverse natural course and successful treatment with combination immunosuppression. Blood 1981;57:267–276.

    PubMed  CAS  Google Scholar 

  66. Storb R, Prentice R, Sullivan KM et al. Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow Transplantation from HLA-identical siblings. Ann Intern Med 1983;98:461–466.

    PubMed  CAS  Google Scholar 

  67. McDonald GB, Sullivan KM, Schuffler MD, Shulman HM, Thomas ED. Esophageal abnormalities in chronic graft-versus-host disease in humans. Gastroenterology 1981;80:914–921.

    PubMed  CAS  Google Scholar 

  68. McDonald GB, Sullivan KM, Plumley TP. Radiographic features of esophageal involvement in chronic graft-versus-host disease. Am J Roentgenol 1984;142:501–506.

    CAS  Google Scholar 

  69. Johnston DE, Koehler RE, Balfe DM. Clinical manifestations of epidermolysis bullosa dystrophica. Dig Dis Sci 1981;26:1144–1149.

    Article  PubMed  CAS  Google Scholar 

  70. Agha FP, Raji MR. Esophageal involvement in pemphigoid: Clinical and roentgen manifestations. Gastrointest Radiol 1982;7:109–112.

    Article  PubMed  CAS  Google Scholar 

  71. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man. A long-term clinico-pathologic study of 20 Seattle patients. Am J Med 1980;68:204–217.

    Article  Google Scholar 

  72. Tsoi MS. Immunological mechanisms of graft-versus-host disease in man. Transplantation 1982;33:459–464.

    Article  PubMed  CAS  Google Scholar 

  73. Ralph DD, Springmeyer SC, Sullivan KM et al. Rapidly progressive air flow obstruction in marrow transplant recipients: Possible association between obliterative bronchiolitis and chronic graft-versus-host disease. Am Rev Resp Dis 1984;129:641–644.

    PubMed  CAS  Google Scholar 

  74. Schubert MM, Sullivan KM, Morton TH et al. Oral manifestations of chronic graft-versus-host disease. Arch Intern Med 1984;144:1591–1595.

    Article  PubMed  CAS  Google Scholar 

  75. Yau JC, Zander AR, Srigley JR et al. Chronic graft-versus-host disease complicated by mi-cronodular cirrhosis and esophageal varices. Transplantation 1986;41:129–130.

    Article  PubMed  CAS  Google Scholar 

  76. Knapp AB, Crawford JM, Rappeport JM, Gollan JL. Cirrhosis as a consequence of graft-versus-host disease. Gastroenterology 1987;92:513–519.

    PubMed  CAS  Google Scholar 

  77. McDonald GB, Sharma P, Matthews DE et al. Venocclusive disease of the liver after bone marrow Transplantation: Diagnosis, incidence, and predisposing factors. Hepatology 1984;4:116–122.

    Article  PubMed  CAS  Google Scholar 

  78. Wulff JC, Santner TJ, Storb R et al. Transfusion requirements after HLA-identical marrow Transplantation in 82 patients with aplastic anemia. Vox Sang 1983;44:366–374.

    Article  PubMed  CAS  Google Scholar 

  79. Poulsen H, Christoffersen P. Abnormal bile duct epithelium in chronic aggressive hepatitis and cirrhosis. Hum Pathol 1972;3:217–225.

    Article  PubMed  CAS  Google Scholar 

  80. Bianchi L, Desmet VJ, Popper H et al. Histologic patterns of liver disease in hemophiliacs, with special reference to morphologic characteristics of non-A, non-B hepatitis. Semin Liv Dis 1987;7:203–209.

    Article  CAS  Google Scholar 

  81. Izutsu KT, Sullivan KM, Schubert MM et al. Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease. Transplantation 1983;35:441–446.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology/Hepatology Section, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington, 98104, USA

    George B. McDonald

Authors
  1. George B. McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Calgary, Calgary, Alberta, Canada

    Eldon Shaffer M.D.

  2. The University of Alberta, Edmonton, Alberta, Canada

    Alan B. R. Thomson M.D., Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Publishing Corporation

About this chapter

Cite this chapter

McDonald, G.B. (1989). Immunological Injury to the Intestine and Liver in Human Marrow Transplant Recipients. In: Shaffer, E., Thomson, A.B.R. (eds) Modern Concepts in Gastroenterology Volume 2. Topics in Gastroenterology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0781-5_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0781-5_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8079-8

  • Online ISBN: 978-1-4613-0781-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation