Seminars in Hematology
Volume 37, Issue 3 , Pages 239-248 , July 2000

Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura

  • Robert McMillan

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Robert McMillan, MD, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA92037.

References 

  1. Ballem PJ, Segal GM, Stratton JR, et al.  Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence for both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80:33–40
  2. Beardsley DS, Spiegel JE, Jacobs MM, et al.  Platelet membrane glycoprotein IIIa contains target antigens that bind antiplatelet antibodies in immune thrombocytopenias. J Clin Invest. 1984;74:1701–1707
  3. Berchtold P, Muller D, Beardsley D, et al.  International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies. Br J Haematol. 1997;96:477–483
  4. Berchtold P, Wenger M. Autoantibodies against platelet glycoproteins in autoimmune thrombocytopenic purpura: Their clinical significance and response to treatment. Blood. 1993;81:1246–1250
  5. Bowditch RD, Tani P, Fong KC, et al.  Characterization of autoantigenic epitopes on platelet glycoprotein IIb/IIIa using random peptide libraries. Blood. 1996;88:4579–4584
  6. Bowditch RD, Tani P, McMillan R. Reactivity of autoantibodies from chronic ITP patients with recombinant glycoprotein IIIa peptides. Br J Haematol. 1995;91:178–184
  7. Brighton TA, Evans S, Castaldi PA, et al.  Prospective evaluation of the clinical usefulness of an antigen-specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Blood. 1996;88:194–201
  8. Chang M, Nakagawa PA, Schwartz M, et al.  Effects of immune thrombocytopenic purpura (ITP) patient plasma on in vitro megakaryocytopoiesis. Blood. 1999;94(suppl 1):646a; abstr
  9. Christie DJ, Sauro SC, Fairbanks KD, et al.  Detection of clonal platelet antibodies in immunologically-mediated thrombocytopenias: Association with circulating clonal/oligclonal B cells. Br J Haematol. 1993;85:277–284
  10. Cierniewski SS, Haas TA, Smith JW, et al.  Characterization of cation-binding sequences in the platelet integrin GPIIb-IIIa (αIIbβ3) by terbium luminescence. Biochemistry. 1994;33:12238–12246
  11. Cines DB, Schreiber AD. Immune thrombocytopenia: Use of a Coombs antiglobulin test to detect IgG and C3 on platelets. N Engl J Med. 1979;300:106–111
  12. Clarkson SB, Bussel JB, Kimberly RP, et al.  Treatment of refractory immune thrombocytopenic purpura with anti-Fcgreceptor antibody. N Engl J Med. 1986;314:1236–1239
  13. D'Souza SE, Haas TA, Piotrowicz RS, et al.  Ligand and cation binding are dual functions of a discrete segment of the integrin β3 subunit: Cation displacement is involved in ligand binding. Cell. 1994;79:659–667
  14. Dixon R, Rosse W, Ebbert L. Quantitative determination of antibody in idiopathic thrombocytopenic purpura: Correlation of serum and platelet-bound antibody with clinical response. N Engl J Med. 1975;292:230–236
  15. Escher R, Muller D, Vogel M, et al.  Recombinant human natural autoantibodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP. Br J Haematol. 1998;102:820–828
  16. Fabris F, Cordiano I, Steffan A, et al.  Identification of anti-platelet autoantibodies by Western blot in 45 patients with idiopathic thrombocytopenic purpura (ITP). Haematologica. 1993;77:122–126
  17. Fehr J, Hofmann V, Kappeler U. Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gammaglobulin. N Engl J Med. 1982;306:1254–1258
  18. Firkin BG, Wright R, Miller S, et al.  Splenic macrophages in thrombocytopenia. Blood. 1969;33:240–245
  19. Frank MM, Schreiber AD, Atkinson JP, et al.  Pathophysiology of immune hemolytic anemia. Ann Intern Med. 1977;87:210–222
  20. Fujisawa K, McMillan R. Platelet-associated antibody to glycoprotein IIb/IIIa from chronic immune thrombocytopenic purpura patients often binds to divalent cation-dependent antigens. Blood. 1993;81:1284–1289
  21. Fujisawa K, O'Toole TE, Tani P, et al.  Autoantibodies to the presumptive cytoplasmic domain of platelet glycoprotein IIIa in patients with chronic immune thrombocytopenic purpura. Blood. 1991;77:2207–2213
  22. Fujisawa K, Tani P, O'Toole TE, et al.  Different specificities of platelet-associated and plasma autoantibodies to platelet GPIIb-IIIa in patients with chronic ITE. Blood. 1992;79:1441–1446
  23. Fujisawa K, Tani P, Piro L, et al.  The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura. Blood. 1993;81:2872–2877
  24. Gearhart CG, Sigal NH, Klinman NR. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. In: ed 5. Proc Natl Acad Sci USA. 72:1975;p. 1707–1711
  25. George JN. Platelet immunoglobulin G: Its significance for the evaluation of thrombocytopenia and for understanding the origin of a-granule proteins. Blood. 1990;76:859–870
  26. George JN, El-Harake MA, Aster RH. Thrombocytopenia due to enhanced platelet destruction by immunologic mechanisms. In:  Beuder E,  Lichtman MA,  Coller BS, et al. editor. Williams Hematology. ed 5. New York, NY: McGraw-Hill; 1995;p. 1315–1355
  27. Handin RI, Stossel TP. Phagocytosis of antibody-coated platelets by human granulocytes. N Engl J Med. 1974;290:989–993
  28. Harrington WJ, Sprague CC, Minnich V, et al.  Immunologic mechanisms in idiopathic and neonatal thrombocytopenic purpura. Ann Intern Med. 1953;38:433–469
  29. Hauch TW, Rosse WF. Platelet-bound complement (C3) in immune thrombocytopenia. Blood. 1977;50:1129–1136
  30. He R, Reid DM, Jones CE, et al.  Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura. Blood. 1994;83:1024–1032
  31. He R, Reid DM, Jones CE, et al.  Extracellular epitopes of platelet glycoprotein Ibα reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura. Blood. 1995;86:3789–3796
  32. Heyns AP, Badenhorst PN, Lotter MG, et al.  Platelet turnover and kinetics in immune thrombocytopenic purpura: Results with autologous 111-In-labeled and homologous 51-Cr-labeled platelets differ. Blood. 1986;67:86–92
  33. Heyns AP, Lotter MG, Badenhorst PN, et al.  Kinetics and sites of destruction of 111-Indium-oxine-labeled platelets in idiopathic thrombocytopenic purpura: A quantitative study. Am J Hematol. 1982;12:167–177
  34. Honda S, Tomiyama Y, Pelletier AJ, et al.  Topography of ligand-induced binding sites, including a novel cationsensitive epitope (AP5) at the amino terminus, of the human integrin β3 subunit. J Biol Chem. 1995;270:11947–11954
  35. Hou M, Stockelberg D, Kutti J, et al.  Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1995;91:971–975
  36. Hymes K, Schur PH, Karpatkin S. Heavy-chain subclass of bound antiplatelet IgG in autoimmune thrombocytopenic purpura. Blood. 1980;56:84–87
  37. Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997;349:1531–1536
  38. Kayser W, Mueller-Eckhardt C, Bhakdi S, et al.  Platelet-associated complement C3 in thrombocytopenic states. Br J Haematol. 1983;54:353–363
  39. Kekomaki R, Dawson B, McFarland J, et al.  Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa. J Clin Invest. 1991;88:847–854
  40. Kelton JG, Gibbons S. Autoimmune platelet destruction: Idiopathic thrombocytopenic purpura. In: ed 2. Semin Thromb Haemost. 8:1982;p. 83–104
  41. Kelton JG, Powers PJ, Carter CJ. A prospective study of the usefulness of the measurement of platelet-associated IgG for the diagnosis of idiopathic thrombocytopenic purpura. Blood. 1982;60:1050–1053
  42. Kiefel V, Santoso S, Kaufmann E, et al.  Autoantibodies against platelet glycoprotein Ib/Ix: A frequent finding in autoimmune thrombocytopenic purpura. Br J Haematol. 1991;79:256–262
  43. Kiefel VJ, Santoso S, Weisheit M, et al.  Monoclonal antibody-specific immobilization of platelet antigens (MAIPA): A new tool for the identification of platelet-reactive antibodies. Blood. 1987;70:1722–1726
  44. Kosugi S, Tomiyama Y, Shiraga M, et al.  Platelet-associated anti-glycoprotein (GP) IIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura mainly recognize cation-dependent conformations: Comparison with the epitopes of serum autoantibodies. Thromb Haemost. 1996;75:339–345
  45. Kurata Y, Curd JG, Tamerius JD, et al.  Platelet-associated complement in chronic ITP. Br J Haematol. 1985;60:723–733
  46. Lynch DM, Howe SE. Antigenic determinants in idiopathic thrombocytopenic purpura. Br J Haematol. 1986;63:301–308
  47. McMillan R, Bowditch R, Tani P, et al.  A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa autoantibody. Br J Haematol. 1996;95:747–749
  48. McMillan R, Bowditch R, Tani P, et al.  An autoantibody which blocks ligand binding to platelet GPIIb/IIIa binds to an epitope on glycoprotein IIb. Blood. 1999;94(suppl 1):13a; abstr
  49. McMillan R, Imbach P. Immune thrombocytopenia. In:  Schafer J,  Loscalzo AI editor. Thrombosis and Hemorrhage. ed 2. Cambridge, MA: Blackwell Scientific; 1998;p. 643–664
  50. McMillan R, Longmire RL, Tavassoli M, et al.  In vitro platelet phagocytosis by ITP splenic leukocytes in idiopathic thrombocytopenic purpura. N Engl J Med. 1974;290:249–251
  51. McMillan R, Lopez-Dee J. Clonal restriction of platelet-associated autoantibodies (PAAb) to platelet glycoprotein (GP) IIb/IIIa. Blood. 1999;94(suppl 1):15a; abstr
  52. McMillan R, Luiken GA, Levy R, et al.  Antibody against megakaryocytes in idiopathic thrombocytopenic purpura. JAMA. 1978;239:2460–2462
  53. McMillan R, Smith RS, Longmire RL, et al.  Immunoglobins associated with human platelets. Blood. 1971;37:316–322
  54. McMillan R, Tani P, Millard F, et al.  Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP. Blood. 1987;70:1040–1045
  55. Mueller-Eckhardt C, Mueller-Eckhardt G, Kayser W, et al.  Platelet-associated IgG, pktelet survival, and platelet sequestration in thrombocytopenic states. Br J Haematol. 1982;52:49–58
  56. Nardi MA, Liu L, Karpatkin S. GPIIIa-(49–66) is a major pathophysiologically relevant antigenic determinant for antiplatelet GPIIIa of HIV-1-related immunologic thrombocytopenia. In: Proc Nad Acad Sci USA. 94:1997;p. 7589–7594
  57. Nugent D. Human monoclonal antibodies in the characterization of platelet antigens. In:  Kunicki T,  George JN editor. Platelet Immunobiology: Molecular and Clinical Aspects. Philadelphia, PA: Lippincott; 1989;p. 273–290
  58. Reid DM, Jones CE, Vostal JG, et al.  Western blot identification of platelet proteins that bind normal serum immunoglobulins. Characteristics of a 95 Kd reactive protein. Blood. 1990;75:2194–2203
  59. Rosse WF, Adams JP, Yount WJ. Subclasses of IgG antibodies in immune thrombocytopenic purpura. Br J Haematol. 1980;46:109–114
  60. Salama A, Kiefel V, Mueller-Eckhardt C. Effect of IgG anti-Rho(D) in adult patients with chronic autoimmune thrombocytopenia. Am J Hematol. 1986;22:241–250
  61. Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura: Physiologic, serologic, and isotopic studies. Ann NY Acad Sci. 1965;124:499–542
  62. Shulman NR, Weinrach RS, Libre EP, et al.  The role of the reticuloendothelial system in the pathogenesis of idiopathic thrombocytopenic purpura. Trans Assoc Am Physicians. 1965;78:374–390
  63. Sinha RK, Kelton JG. Current controversies concerning the measurement of platelet-associated IgG. Transfus Med Rev. 1990;4:121–135
  64. Stockelberg D, Hou M, Jacobsson S, et al.  Evidence for a light chain restriction of glycoprotein Ib/IX and IIb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1995;90:175–179
  65. Stockelberg D, Hou M, Jacobsson S, et al.  Light chainrestricted autoantibodies in chronic idiopathic thrombocytopenic purpura, but no evidence for circulating clonal B-lymphocytes. Ann Hematol. 1996;72:29–34
  66. Stoll D, Cines DB, Aster RH, et al.  Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. Blood. 1985;65:584–588
  67. Stossel TP. Phagocytosis. N Engl J Med. 1974;290:717–723
  68. Tani P, Berchtold P, McMillan R. Autoantibodies in chronic ITP. Blut. 1989;59:44–46
  69. Tavassoli M, McMillan R. Structure of the spleen in idiopathic thrombocytopenic purpura. Am J Clin Pathol. 1975;64:180–191
  70. Tijhuis GJ, Klaassen L, Modderman PW, et al.  Quantification of platelet-bound immunoglobulins of different class and subclass using radiolabelled monoclonal antibodies: assay conditions and clinical application. Br J Haematol. 1991;77:93–101
  71. Tsubakio T, Kurata Y, Kanayama Y, et al.  In vitro platelet phagocytosis in idiopathic thrombocytopenic purpura. Acta Haematol. 1983;70:250–256
  72. Tsubakio T, Tani P, Curd JG, et al.  Complement activation in vitro by antiplatelet antibodies in chronic immune thrombocytopenic purpura. BrJ Haematol. 1986;63:293–300
  73. Vainchenker W, Deschamps JF, Bastin JM, et al.  Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: Immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in in vivo cells from normal and leukemic patients. Blood. 1982;59:514–521
  74. Van der Harst D, de Jong D, Limpens J, et al.  Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura. Blood. 1990;76:2321–2326
  75. van Leeuwen EF, van der Ven JTH, Engelfriet CP, et al.  Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982;59:23–26
  76. Varon D, Karpatkin S. A monoclonal antiplatelet antibody with decreased reactivity for autoimmune thrombocytopenic platelets. In: Proc Nad Acad Sci USA. 80:1983;p. 6992–6995
  77. Warrier I, Moore JE, Warkentin TE, et al.  A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura. Br J Haematol. 1999;104:442–447
  78. Woods VL, Kurata Y, Montgomery RR, et al.  Autoantibodies against platelet glycoprotein Ib in patients with chronic idiopathic thrombocytopenic purpura. Blood. 1984;64:156–160
  79. Woods VL, Oh EH, Mason D, et al.  Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITE. Blood. 1984;63:368–375
  80. Woods VL, Wolff LE, Keller DM. Resting platelets contain a substantial centrally located pool of glycoprotein Ilb-IIIa complex which may be accessible to some but not other extracellular proteins. J Biol Chem. 1986;261:15242–15251

☆ Supported by Grant No, HL61809 from the National Institutes of Health.

PII: S0037-1963(00)90102-1

Seminars in Hematology
Volume 37, Issue 3 , Pages 239-248 , July 2000

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