European Journal of Pediatrics

, Volume 154, Supplement 4, pp S60–S64

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity

  • P. Imbach
  • J. Akatsuka
  • V. Blanchette
  • A. Burek-Kozlowska
  • J. Bussel
  • G. Gaedicke
  • A. Gianella-Borradori
  • E. Gugler
  • A. Hirt
  • B. Imholz
  • R. McMillan
  • A. Morell
  • A. Newland
  • D. Nugent
  • M. H. Schöni
  • H. P. Wagner
Living Pediatrics Symposium in Honour of the 80th Birthday of Professor E. Rossi, Berne, Switzerland

Abstract

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP.

Key words

Immune thrombocytopenic purpura Auto-antibodies Against platelets Immunoglobulin 

Abbreviations

ITP

immune thrombocytopenic purpura

IVIG

intravenous immunoglobulin

References

  1. 1.
    Akatsuka, J, Fujisawa K, Ishidoya N, et al. (1989) Long-term follow-up study of children with chronic ITP. Blut 59: 105–108PubMedGoogle Scholar
  2. 2.
    Anderson JC (1994) Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med 330: 1560–1564PubMedGoogle Scholar
  3. 3.
    Andresson JP, Andersson UG (1990) Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 71:372–376PubMedGoogle Scholar
  4. 4.
    Andrew M, Blanchette VS, Adams M, et al. (1991) A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. J Pediatr 120:522–527Google Scholar
  5. 5.
    Battaieb A, Oksenhendler E, Fromont P, et al. (1989) Immunochemical analysis of platelet auto-antibodies in HIV-related thrombocytopenic purpura: a study of 68 patients. Br J Haematol 73:241–247PubMedGoogle Scholar
  6. 6.
    Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M, Chan KW, Esseltine D, de Veber B, Israels S, Kobrinsky N, Luke B (1994) Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet 344:703–707PubMedGoogle Scholar
  7. 7.
    Cornelius A, Campbell D, Schwart E, Poncz M (1991) Elevated common acute lymphoblastic antigen expression in pediatric immune thrombocytopenic purpura. Am J Pediatr Hematol Oncol 13:57PubMedGoogle Scholar
  8. 8.
    Dammacco F, Jodice G, Campobasso N (1986) Treatment of adult patients with ITP with intravenous immunoglobulin; effect on T cell subsets and PWM induced antibody synthesis in vitro. Br J Haematol 62:125–135PubMedGoogle Scholar
  9. 9.
    Dwyer JM (1992) Manipulating the immune system with immune globulin. N Engl J Med 326:107–116PubMedGoogle Scholar
  10. 10.
    Fateh-Moghadem A, Wick M, Besinger U, Geursen RC (1984) High dose intravenous gammaglobulin for myasthenia gravis. Lancet I:848–849Google Scholar
  11. 11.
    Fehr J, Hofmann V, Kappeler U (1982) Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high dose intravenous gammaglobulin. N Engl J Med 206: 1254–1258Google Scholar
  12. 12.
    Griffin DE, Moench TR, Johnston RT, et al. (1986) Peripheral blood mononuclear cells during natural measles virus infection: cell surface phenotypes and evidence for activation. Clin Immunol Immunopathol 40:305–312PubMedGoogle Scholar
  13. 13.
    Imbach P, Barandun S, d'Apuzzo V, et al. (1986) High-dose intravenous gamma-globulin for idiopathic thrombocytopenic purpura in childhood. Lancet I:1228–1231Google Scholar
  14. 14.
    Imbach P, Wagner HP, Berchtold W, et al. (1985) Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet II:464–468Google Scholar
  15. 15.
    Imbach P, Tani P, McMillan R, et al. (1991) Different forms of chronic ITP in children defined by antiplatelet autoantibodies. J Pediatr 118:535–539PubMedGoogle Scholar
  16. 16.
    Imholz B, Imbach P, Baumgartner C, et al. (1985) Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet 56:63–68Google Scholar
  17. 17.
    Karpatkin S, Nardi M, Lennette ET, et al. (1988) Antihuman immunodeficiency virus type 1 antibody complexes on plate- lets of seropositive thrombocytopenic homosexuals and narcotic addicts. Proc Natl Acad Sci USA 85:9763–9767PubMedGoogle Scholar
  18. 18.
    Kurtzman G, Frickhofen N, Kimbali J, et al. (1989) Pure red-cell aplasia of 10 years' duration due t persistent parvovirus B 19 infection and its cure with immunoglobulin therapy. N Engl J Med 321:519–523PubMedGoogle Scholar
  19. 19.
    Leung DYM, Cotran RS, Kurf-Jones E, Burns JC, Newburger JW, Pober JS (1989) Endothelial cell activation and high interleukin-secretion in the pathogenesis of acute Kawasaki disease. Lancet (:1298–1302Google Scholar
  20. 20.
    McGuire WA, Yang HH, Bruno E, et al. (1987) Treatment of antibody mediated pure red cell aplasia with high dose intravenous gammaglobulin. N Engl J Med 317:1004–1008Google Scholar
  21. 21.
    McMillan R, Tani P, Millard F, et al. (1987) Platelet-accoxiated and plasma antiglycoprotein auto-antibodies in chronic ITP. Blood 70:1040–1045PubMedGoogle Scholar
  22. 22.
    McVerry BA, Spearing R, Smith A (1985) SLE anticoagulant; transient inhibition by high dose immunoglobulin infusion. Br J Hematol 9:49–58Google Scholar
  23. 23.
    NIH Consensus Conference (1990) Intravenous immune globulin: prevention and treatment of disease JAMA 264: 3189–3193Google Scholar
  24. 24.
    Nugent D, English M, Hawkins D, Pendergrass T, Tarantino M (1994) High dose dexamethasone therapy for pediatric patients with retradory immune-mediated thrombocytopenic purpura (ITP). Blood 94 [Suppl. 1]:186A (Abstract No. 731)Google Scholar
  25. 25.
    Rhodes G, Rumpold H, Kurki P, et al. (1987) Autoantibodies in infectious mononucleosis have specificity for the glycine-alanine repeating region of the Epstein-Barr virus nuclear antigen. J Exp Med 165:1026–1040PubMedGoogle Scholar
  26. 26.
    Ross C, Hansen MB, Schyberg T, Berk K (1990) Autoantibodies to crude human leukocyte interferon (IFN), native human IFN, recombinant human IFN alpha 2b and human IFN gamma in healthy blood donors. Clin Ecp Immunol 32:695–701Google Scholar
  27. 27.
    Sandilands GP, althrah HI, Templeton G, et al. (1987) In vivo and in vitro blocking of human lymphocyte Fc receptors by intravenous gammaglobulin. J Clin Lab Immunol 23:109–115PubMedGoogle Scholar
  28. 28.
    Semple JW, Freedman J (1991) Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia. Blood 78: 2619–2625PubMedGoogle Scholar
  29. 29.
    Sing GK, Ruscetti FW (1990) Preferential suppression of myelopoiesis in normal human bone marrow cells after in vitro challenge with human cytomegalovirus. Blood 25:159–172Google Scholar
  30. 30.
    Sultan Y, Kazatchkine MD, Maisonneuve P, Nydegger UE (1985) Antiidiotypic suppression of auto-antibodies to factor VIII anti-hemophilic factor by high dose intravenous gammaglobulin. Lancet II:765–768Google Scholar
  31. 31.
    Tamary H, Kaplinsky C, Levy I, Cohen IJ, Yaniv I, Stark B, Goshen Y, zaizov R (1994) Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up. Acta Pediatr 83: 931–934Google Scholar
  32. 32.
    Van der Harst D, de Jong D, Limpens J, et al. (1990) Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura. Blood 76:2321–2326PubMedGoogle Scholar
  33. 33.
    Van der Lelie J, Lange JMA, Vos JJE, et al. (1987) Autoimmunity against blood cells in human immunodeficiency virus (HIV) infection. Br J Haematol 67:109–114PubMedGoogle Scholar
  34. 34.
    Walsh CM, Nardi MA, Karpatkin S (1984) On the mechanism of thrombocytopenic purpura in sexually active homosexual men. N Engl J Med 311: 635–639PubMedGoogle Scholar
  35. 35.
    Young N (1990) Hematologic and hematopoietic consequences of B19 parvovirus infection. Semin Hematol 25:159–172Google Scholar
  36. 36.
    Young N, Mortimer P (1984) Viruses and bone marrow failure. Blood 63: 729–737PubMedGoogle Scholar
  37. 37.
    Gianella-Borradori A, Hirt A, Lüthi A, Wagner HP, Imbach P (1994) Haemophilia due to factor VIII inhibitors in a patient suffering from an autoimmune disease: Treatment with intravenous immunoglobulin; a case report. Blut 48:409–413Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • P. Imbach
    • 1
    • 2
  • J. Akatsuka
    • 3
  • V. Blanchette
    • 4
  • A. Burek-Kozlowska
    • 5
  • J. Bussel
    • 6
  • G. Gaedicke
    • 7
  • A. Gianella-Borradori
    • 8
  • E. Gugler
    • 9
  • A. Hirt
    • 9
  • B. Imholz
    • 9
  • R. McMillan
    • 10
  • A. Morell
    • 5
  • A. Newland
    • 11
  • D. Nugent
    • 12
  • M. H. Schöni
    • 13
  • H. P. Wagner
    • 9
  1. 1.Kinderklinik AarauAarauSwitzerland
  2. 2.Universitäts-KinderspitalBaselSwitzerland
  3. 3.The Daisan HospitalTokyoJapan
  4. 4.Hospital for Sick ChildrenToronto 10Canada
  5. 5.Central LaboratorySRKBerneSwitzerland
  6. 6.Cornell UniversityNew YorkUSA
  7. 7.Universitäts-Kinderklinik CharlottenburgBerlinGermany
  8. 8.SandozBaselSwitzerland
  9. 9.Kinderklinik InselspitalBernSwitzerland
  10. 10.Scripps ClinicLa JollaU.S.A.
  11. 11.The London HospitalLondonU.K.
  12. 12.Children's HospitalOrangeUSA
  13. 13.Alpine Children's HospitalDavosSwitzerland

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