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Autoantigens in ITP

  • Yoshiaki TomiyamaEmail author
Chapter

Abstract

Antiplatelet autoantibodies play a critical role in autoimmune thrombocytopenia (ITP). Thus, characterization of autoantigens recognized by autoantibodies is a prerequisite for elucidating its pathophysiology. Platelet glycoprotein (GP) IIb-IIIa and/or GPIb-IX are the two major autoantigens in ITP. This capture reviews recent advance in the characterization and localization of autoantigens in ITP.

Keywords

Autoimmune Hemolytic Anemia Direct Antiglobulin Test Platelet Destruction Autoimmune Thrombocytopenia Platelet Antigen 
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.

Notes

Acknowledgment

This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan and the Ministry of Health, Labour and Welfare in Japan.

References

  1. 1.
    McMillan R. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1981;304:1135–47.CrossRefPubMedGoogle Scholar
  2. 2.
    George JN, El-Harase MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1994;331:1207–11.CrossRefPubMedGoogle Scholar
  3. 3.
    Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997;349:1531–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995–1008.CrossRefPubMedGoogle Scholar
  5. 5.
    Kashiwagi H, Tomiyama Y. Pathophysiology and management of primary immune thrombocytopenia. Int J Hematol. 2013;98:24–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38:1–10.PubMedGoogle Scholar
  7. 7.
    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 N Y Acad Sci. 1965;124:499–542.CrossRefPubMedGoogle Scholar
  8. 8.
    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;60:1050–3.PubMedGoogle Scholar
  9. 9.
    Mueller-Eckhardt C, Kayser W, Mersch-Baumert K, Mueller-Eckhardt G, Breidenbach M, Kugel HG, et al. The clinical significance of platelet-associated IgG: a study on 298 patients with various disorders. Br J Haematol. 1980;46:123–31.CrossRefPubMedGoogle Scholar
  10. 10.
    George JN, Caen JP, Nurden AT. Glanzmann’s thrombasthenia: the spectrum of clinical disease. Blood. 1990;75:1383–95.PubMedGoogle Scholar
  11. 11.
    Tomiyama Y. Glanzmann thrombasthenia: integrin αIIbβ3 deficiency. Int J Hematol. 2000;72:448–54.PubMedGoogle Scholar
  12. 12.
    van Leeuwen EF, van der Ven JTJ, Engelfreit CP, von dem Borne AE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982;59:23–6.PubMedGoogle Scholar
  13. 13.
    Woods Jr VL, Oh EH, Mason D, McMillan R. Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP. Blood. 1984;63:368–75.PubMedGoogle Scholar
  14. 14.
    McMillan R, Tani P, Millard F, Berchtold P, Renshow L, Woods Jr VL. Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP. Blood. 1987;70:1040–5.PubMedGoogle Scholar
  15. 15.
    Kiefel V, Santoso S, Kaufmann E, Mueller-Eckhardt C. Autoantibodies against platelet glycoprotein Ib/IX: a frequent finding in autoimmune thrombocytopenic purpura. Br J Haematol. 1991;79:256–62.CrossRefPubMedGoogle Scholar
  16. 16.
    Tomiyama Y, Take H, Honda S, Furubayashi T, Mizutani H, Tsubakio T, et al. Demonstration of platelet antigens that bind platelet-associated autoantibodies in chronic ITP by direct immunoprecipitation procedure. Br J Haematol. 1990;75:92–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Tomiyama Y, Kosugi S. Autoantigenic epitopes on platelet glycoproteins. Int J Hematol. 2005;81:100–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Brighton TA, Evans S, Castaldi PA, Chesterman CN, Chong BH. Prospective evaluation of the clinical usefulness of an antigenspecific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Blood. 1996;88:194–201.PubMedGoogle Scholar
  19. 19.
    McMillan R, Wang L, Tani P. Prospective evaluation of the immunobead assay for the diagnosis of adult chronic immune thrombocytopenic purpura (ITP). J Thromb Haemost. 2003;1:485–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Fujisawa K, Tani P, Piro L, McMillan R. The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura. Blood. 1993;81:2872–7.PubMedGoogle Scholar
  21. 21.
    Tani P, Berchtold P, McMillan R. Autoantibodies in chronic ITP. Blut. 1989;59:44–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Beardsley DS, Spiegel JE, Jacobs MM, Handin RI, Lux SE. Platelet membrane glycoprotein IIIa contains target antigens that bind anti-platelet antibodies in immune thrombocytopenias. J Clin Invest. 1984;74:1701–7.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tomiyama Y, Kurata Y, Mizutani H, et al. Platelet glycoprotein IIb as a target antigen in two patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1987;66:535–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Fujisawa K, O’Tool TE, Tani P, et al. Autoantibodies to the presumptive cytoplasmic domain of platelet glycoprotein IIIa in patients with chronic immune thrombocytopenic purpura. Blood. 1991;77:2207–13.PubMedGoogle Scholar
  25. 25.
    Fujisawa K, Tani P, O’Toole TE, Ginsberg MH, McMillan R. Different specificities of platelet-associated and plasma autoantibodies to platelet GPIIb-IIIa in patients with chronic immune thrombocytopenic purpura. Blood. 1992;79:1441–6.PubMedGoogle Scholar
  26. 26.
    Kosugi S, Tomiyama Y, Shiraga M, et al. Platelet-associated antiglycoprotein (GP) IIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura mainly recognize cation-dependent conformations: comparison with the epitopes of serum autoantibodies. Thromb Haemost. 1996;75:339–45.PubMedGoogle Scholar
  27. 27.
    Kosugi S, Tomiyama Y, Honda S, et al. Anti-αvβ3 antibodies in chronic immune thrombocytopenic purpura. Thromb Haemost. 2001;85:36–41.PubMedGoogle Scholar
  28. 28.
    Tomiyama Y, Kekomäki R, McFarland J, Kunicki TJ. Antivinculin antibodies in sera of patients with immune thrombocytopenia and in sera of normal subjects. Blood. 1992;79:161–8.PubMedGoogle Scholar
  29. 29.
    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;81:1284–9.PubMedGoogle Scholar
  30. 30.
    Bowditch RD, Tani P, McMillan R. Reactivity of autoantibodies from chronic ITP patients with recombinant glycoprotein IIIa peptides. Br J Haematol. 1995;91:178–84.CrossRefPubMedGoogle Scholar
  31. 31.
    Loftus JC, O’Tool TE, Plow EF, Glass A, Frelinger III AL, Ginsberg MH. A β3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science. 1990;249:915–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Honda S, Tomiyama Y, Shiraga M, et al. A two amino acid insertion in the Cys46-Cys167 loop of the αIIb subunit is associated with a variant of Glanzmann thrombasthenia. J Clin Invest. 1998;102:1183–92.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Kosugi S, Tomiyama Y, Honda S, et al. Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of glycoprotein (GP) IIb. Blood. 2001;98:1819–27.CrossRefPubMedGoogle Scholar
  34. 34.
    Kiyomizu K, Kashiwagi H, Nakazawa T, et al. Recognition of highly restricted regions in the β-propeller domain of αIIb by platelet-associated anti-αIIbβ3 autoantibodies in primary immune thrombocytopenia. Blood. 2012;120:1499–509.CrossRefPubMedGoogle Scholar
  35. 35.
    McMillan R, Wang L, Lopez-Dee J, Jiu S, Loftus JC. Many αIIbβ3 autoepitopes in chronic immune thrombocytopenic purpura are localized to αIIb between amino acids L1 and Q459. Br J Haematol. 2002;118:1132–6.CrossRefPubMedGoogle Scholar
  36. 36.
    McMillan R, Lopez-Dee J, Bowditch R. Clonal restriction of platelet-associated anti-GPIIb/IIIa autoantibodies in patients with chronic ITP. Thromb Haemost. 2001;85:821–3.PubMedGoogle Scholar
  37. 37.
    Roark JH, Bussel JB, Cines DB, Siegel DL. Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation. Blood. 2002;100:1388–98.PubMedGoogle Scholar
  38. 38.
    He R, Reid DM, Jones CE, Shulman NR. Extracellular epitopes of platelet glycoprotein Ibα reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura. Blood. 1995;86:3789–96.PubMedGoogle Scholar
  39. 39.
    Nardi MA, Liu LX, Karpatkin S. GPIIIa-(49-66) is a major pathophysiologically relevant antigenic determinant for anti-platelet GPIIIa of HIV-1-related immunologic thrombocytopenia. Proc Natl Acad Sci U S A. 1997;94:7589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Chouhan B, Denesyuk A, Heino J. Conservation of the human integrin-type β-propeller domain in bacteria. PLoS One. 2011;6(10):e25069.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Blood TransfusionOsaka University HospitalSuitaJapan

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