Transfusion Medicine Reviews
Volume 17, Issue 1 , Pages 69-80 , January 2003

Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update

  • Malini D. Coopamah

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital Toronto, Ontario Canada
    • Department of Pharmacology, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Medicine, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Canadian Blood Services, Toronto, Ontario Canada
    • Toronto Platelet Immunobiology Group, Toronto, Ontario Canada
    • ,
  • M. Bernadette Garvey

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital Toronto, Ontario Canada
    • Department of Pharmacology, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Medicine, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Canadian Blood Services, Toronto, Ontario Canada
    • Toronto Platelet Immunobiology Group, Toronto, Ontario Canada
    • ,
  • John Freedman

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital Toronto, Ontario Canada
    • Department of Pharmacology, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Medicine, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Canadian Blood Services, Toronto, Ontario Canada
    • Toronto Platelet Immunobiology Group, Toronto, Ontario Canada
    • ,
  • John W. Semple

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital Toronto, Ontario Canada
    • Department of Pharmacology, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Medicine, University of Toronto, Canadian Blood Services Toronto, Ontario Canada
    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Canadian Blood Services, Toronto, Ontario Canada
    • Toronto Platelet Immunobiology Group, Toronto, Ontario Canada
    • Corresponding Author InformationAddress reprint requests to John W. Semple, PhD, Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, 30 Bond St, Toronto, ON, Canada, M5B 1W8.

References 

  1. Semple JW, Freedman J. Cellular immune mechanisms in chronic autoimmune thrombocytopenic purpura. Autoimmunity. 1992;13:311–319
  2. Semple JW, Freedman J. Abnormal cellular immune mechanisms associated with autoimmune thrombocytopenia. Transfus Med Rev. 1995;9:327–338
  3. Watts C. Capture and processing of exogenous antigens for presentation on MHC molecules. Annu Rev Immunol. 1997;15:821–850
  4. Chambers CA. The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol. 2001;22:217–223
  5. Elson CJ, Barker RN. Helper T cells in antibody-mediated, organ-specific autoimmunity. Curr Opin Immunol. 2000;12:664–669
  6. Chess L. Blockade of the CD40L/CD40 pathway. In: Austen KF, Burakoff S, Rosen F, Strom T editor. Therapeutic Immunology. ed 2. New York, NY: Blackwell Sciences; 2001;p. 441–456
  7. Mosmann RT, Sad D. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17:138–146
  8. Romangnani S. Th1 and Th2 subsets in human diseases. Clin Immunol Immunopath. 1996;80:225–235
  9. Paliard X, de Waal Malefyt R, Yssel H. simultaneous production of Il-2, Il-4 and INF-γ by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988;141:849–855
  10. Yssel H, de Vries J, de Waal Malefyt R. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol. 1992;149:2378–2384
  11. Coutinho A, Haas W. In vivo models of dominant T-cell tolerance: Where do we stand today?. Trends Immunol. 2001;22:350–351
  12. Kappler JW, Staerz U, White J, et al. Self-tolerance eliminates T cells specific for MLS-modified products of the major histocompatibility complex. Nature. 1988;332:35–40
  13. Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: A costimulatory signaling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480
  14. Goronzy JJ, Weyand M. Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 2001;22:251–255
  15. Jonuleit H, Schmitt E, Steinbrink K, et al. Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol. 2001;22:394–400
  16. Sinha AA, Lopez T, McDevitt HO. Autoimmune diseases: the failure of self-tolerance. Science. 1990;248:1380–1388
  17. Mackay IR. The “autoimmune diseases” 40th anniversary. Autoimmun Rev. 2002;1:5–11
  18. Rosmalen JGM, van Ewijk W, Leenen PJM. T-cell education in autoimmune diabetes: Teachers and students. Trends Immunol. 2002;23:40–46
  19. Doyle HA, Mamula MJ. Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol. 2001;22443-22449:
  20. Wadenvik H, Stockelberg D, Hou M. Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura. Acta Paediatr Suppl. 1998;424:26–36
  21. Mehta YS, Pathare AV, Badakere SS, et al. Influence of auto-antibody specificities on the clinical course in patients with chronic and acute ITP. Platelets. 2000;11:94–98
  22. McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol. 2000;37:239–248
  23. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995–1008
  24. Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94:909–913
  25. Blanchette VS, Semple JW, Freedman J. Intravenous immunoglobulin and Rh immunoglobulin as immunomodulators of autoimmunity to blood elements. In: Silberstein LE editors. Autoimmune Disorders of Blood. Bethesda MD: American Association of Blood Banks; 1996;p. 35–77
  26. Wright JF, Blanchette VS, Wang H, et al. Characterization of platelet-reactive antibodies in children with varicella-associated acute immune thrombocytopenic purpura (ITP). Br J Haematol. 1996;95:145–152
  27. Oldstone MBA. Molecular Mimicry and immune-mediated diseases. FASEB J. 1998;12:1255–1265
  28. (suppl) abstr Chia WK, Blanchette VS, Mody M, et al. Isolation of HIV-1-specific and platelet-crossreactive antibodies from HIV-1-infected thrombocytopenic hemophiliacs. Blood. 1997;90:628
  29. Semple JW, Milev Y, Cosgrave D, et al. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura. Blood. 1996;87:4225–4254
  30. Boshkov LK, Kelton JG, Halloran PF. HLA-DR expression by platelets in acute idiopathic thrombocytopenic purpura. Br J Haematol. 1992;81:552–557
  31. (suppl) abstr Semple JW, Mitelman B, Allen D, et al. Platelet HLA-DR expression is mediated by physical interaction with adherent CD14+ macrophages: Possible role in the pathogenesis of autoimmune thrombocytopenia. Blood. 1995;86:2148
  32. Henn V, Slupsky JR, Grafe M, et al. CD40 ligand on activated platelets triggers an inflammatory reactions of endothelial cells. Nature. 1998;391:591–594
  33. Nomura S, Yanabu M, Kido H, et al. Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura. Eur J Haematol. 1995;55:49–56
  34. Fukuda M. Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem. 1991;266:21327–21330
  35. Schreuder GMT, Tilanus MGJ, Bontrop RE, et al. HLA-DQ polymorphism associated with resistance to type I diabetes detected with monoclonal antibodies, isoelectric point differences, and restriction fragment length polymorphism. J Exp Med. 1986;164:938–943
  36. Karpatkin S. Association of HLA-DRw2 with autoimmune thrombocytopenic purpura. J Clin Invest. 1979;63:1085–1088
  37. El-Khateeb MS, Awidi AS, Tarawneh MS, et al. HLA antigens, blood groups and immunoglobulin levels in idiopathic thrombocytopenic purpura. Acta Haematol. 1986;76:110–114
  38. Goebel KM, Hahn E, Havermann K. HLA matching in autoimmune thrombocytopenic purpura. Br J Haematol. 1977;35:341–342
  39. Porges A, Bussel J, Kimberly R, et al. Elevation of platelet associated antibody levels in patients with chronic idiopathic thrombocytopenic purpura expressing the B8 and/or DR3 allotypes. Tissue Antigens. 1985;26:132–137
  40. Gratama JW, D'Amaro J, deKoning J, et al. The HLA system in immune thrombocytopenic purpura: Its relation to the outcome of therapy. Br J Haematol. 1984;56:287–293
  41. Gaiger A, Neumeister A, Heinzl H, et al. HLA class I and II antigens in chronic idiopathic autoimmune thrombocytopenia. Ann Hematol. 1994;68:299–302
  42. Nomura S, Matsuzaki T, Ozaki Y, et al. Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura. Blood. 1998;91:3616–3622
  43. Kuwana M, Kaburaki J, Pandey JP, et al. HLA class II alleles in Japanese patients with immune thrombocytopenic purpura. Associations with anti-platelets glycoprotein antibodies and responses to splenectomy. Tissue Antigens. 2000;56:337–343
  44. Cao K, Hollenbach J, Shi X, et al. Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations. Hum Imunol. 2001;62:1009–1030
  45. Foster CB, Zhu S, Erichsen HC, et al. Polymorphisms in inflammatory cytokines and Fcgamma receptors in childhood chronic immune thrombocytopenic purpura: A pilot study. Br J Haematol. 2001;113:596–599
  46. Semple JW, Freedman J. Enhanced anti-platelet lymphocyte reactivity in patients with autoimmune thrombocytopenia (AITP). Blood. 1991;78:2619–2625
  47. Ware RR, Howard TA. Phenotypic and clonal analysis of T lymphocytes in childhood immune thrombocytopenic purpura. Blood. 1993;82:2137–2142
  48. Filion MC, Bradley AJ, Devine DV, et al. Autoreactive T cells in healthy individuals show tolerance in vitro with characteristics similar to but distinct from clonal anergy. Eur J Immunol. 1995;25:3123–3127
  49. Shimomura T, Fujimura K, Takafuta T, et al. Oligoclonal accumulation of T cells in peripheral blood from patients with idiopathic thrombocytopenic purpura. B J Haematol. 1996;95:732–737
  50. Kuwana M, Kaburaki J, Ikeda Y. Autoreactive T cells to platelets GPIIbIIIa in immune thrombocytopenic purpura: A role in production of anti-platelet autoantibody. J Clin Invest. 1998;102:1393–1402
  51. Kuwana M, Kaburaki J, Kitasato H, et al. Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura. Blood. 2001;98:130–139
  52. (suppl) abstr Semple JW, Speck ER, Kim M, et al. Characterization and fine specificity of platelet-reactive T cell lines from children with chronic autoimmune thrombocytopenic purpura (AITP). Blood. 2001;98:440a
  53. Kuwana K, Okazaki Y, Kaburaki J, et al. Spleen is the primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura. J Immunol. 2002;168:3675–3682
  54. Garcia-Suarez J, Prieto A, Reyes E, et al. Abnormal γIFN and αTNF secretion in purified CD2+ cells from autoimmune thrombocytopenic purpura patients: Their implication in the clinical course of the disease. Am J Hematol. 1995;49:271–276
  55. Abboud MR, Laver J, Xu F, et al. Serum levels of GM-CSF are elevated in patients with thrombocytopenia. Br J Haematol. 1996;92:486–488
  56. Lazarus AH, Ellis J, Semple JW, et al. Comparison of platelet immunity in patients with SLE and ITP. Transfus Sci. 2000;22:19–27
  57. Yoshimura C, Nomura S, Nagahama M, et al. Plasmasoluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura. Eur J Haematol. 2000;64:219–224
  58. Shenoy S, Mohanakumar T, Chatila T, et al. Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias. Clin Immunol. 2001;99:266–275
  59. Mouzaki A, Theodoropoulou M, Gianakopoulos I, et al. Expression patterns of Th1 and Th2 cytokine genes in childhood idiopathic thrombocytopenic purpura (ITP) at presentation and their modulation by intravenous immunoglobulin G (IVIg) treatment: their role in prognosis. Blood. 2002;100:1774–1779
  60. abstr 0612 Andersson PO, Olsson B, Carlsson B, et al. Gene expression profiling of T lymphocytes in chronic ITP. In: Proc Eur Haematol Assoc Annual Meeting. Italy. 2002;
  61. Crossley AR, Dickinson AM, Proctor SJ, et al. Effects of interferon-alpha therapy on immune parameters in immune thrombocytopenic purpura. Autoimmunity. 1996;24:81–100
  62. Webber NP, Mascarenhas JO, Crow MK, et al. Functional properties of lymphocytes in idiopathic thrombocytopenic purpura. Hum Immunol. 2001;62:1346–1355
  63. Erduran E, Aslan Y, Aliyazicioglu Y, et al. Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura. Am J Hematol. 1998;57:119–123
  64. Tan B, Zhao X, Yin C. Detection of IL-2 receptor in patients with idiopathic thrombocytopenic purpura. Hunan Yi Ke Da Xue Xue Bao. 1998;23:191–193
  65. Andersson PO, Stockelberg D, Jacobsson S, et al. A transforming growth factor-beta 1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura. Ann Hematol. 2000;79:507–513
  66. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Annu Rev Immunol. 1998;16:137–161
  67. Karakantza M, Mouzaki A, Theodoropoulos M, et al. Th1 and Th2 cytokines in a patient with Evan's syndrome and profound lymphopenia. Br J Haematol. 2000;110:968–970
  68. Ziegler ZR, Rosenfield CS, Nemunatis JJ. Increased macrophage colony-stimulating factor levels in immune thrombocytopenic purpura. Blood. 1993;81:1251–1254
  69. Nomura S, Yasunaga K, Fujimura K, et al. High-dose intravenous gamma globulin reduces macrophage colony-stimulating factor levels in idiopathic thrombocytopenic purpura. Int J Hematol. 1996;63:227–234
  70. Baker GR, Levin J. Transient thrombocytopenia produced by administration of macrophage colony-stimulating factor: investigations of the mechanism. Blood. 1998;91:89–99
  71. Lazarus AH, Joy T, Crow AR. Analysis of transmembrane signaling and T cell defects associated with idiopathic thrombocytopenic purpura (ITP). Acta Paediatr Suppl. 1998;424:21–25
  72. Aiura K, Clark BD, Dinarello CA, et al. Interaction with autologous platelets multiplies interleukin-1 and tumor necrosis factor production in mononuclear cells. J Infect Dis. 1997;175:123–129
  73. Lindemann S, Tolley ND, Dixon DA, et al. Activated platelets mediate inflammatory signaling by regulated IL-1β synthesis. J Cell Biol. 2001;154:485–490
  74. suppl (abstr) George J, Raskob G, Lichtin A, et al. Safety and effect on platelets count of a single-dose monoclonal antibody to CD40 ligand (Antnova™) on patients with chronic ITP. Blood. 1998;92:707a
  75. (suppl) abstr Bussel J, Wissert M, Oates B, et al. Humanized monoclonal anti-CD40 ligand antibody (hu5c8) rescue therapy of 15 patients with severe chronic refractory ITP. Blood. 1999;94:646a
  76. suppl (abstr) Kuwana M, Nomura S, Fujimura K, et al. Immunomonitoring after a single injection of humanized monoclonal antibody to CD40 ligand in patients with chronic ITP. Blood. 2001;98:441a
  77. Delgado J, Bustos JG, Jimenez-Yuste V, et al. Anti-CD20 monoclonal antibody therapy in refractory immune thrombocytopenic purpura. Haematologica. 2002;87:215–216
  78. Stasi R, Pagano A, Stipa E, et al. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98:952–957
  79. Hermida G, Manjón R, Casanova M, et al. Oral vaccination with autologous platelets in chronic autoimmune thrombocytopenic purpura. Med Hypotheses. 2001;57:612–615

PII: S0887-7963(03)80006-8

doi: 10.1053/tmrv.2003.50004

Transfusion Medicine Reviews
Volume 17, Issue 1 , Pages 69-80 , January 2003

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