Many αIIbβ3 autoepitopes in chronic immune thrombocytopenic purpura are localized to αIIb between amino acids L1 and Q459

Robert Mcmillan, Lei Wang, Jennifer Lopez-Dee, Sandra Jiu, Joseph C. Loftus

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

In chronic immune thrombocytopenic purpura (ITP), autoantibodies bind to platelet surface proteins, particularly αIIb, resulting in platelet destruction by the reticulo-endothelial system. In order to better localize the autoepitopes on αIIb, we studied the binding of antibodies to Chinese hamster ovary (CHO) cells expressing either αIIbβ3 or αIIbvβ3 chimaeras in which a segment of αIIb (either amino acids L1-Q459, L1-F223 or F223-Q459) was substituted for that portion of αv. We evaluated platelet-associated autoantibodies from 14 ITP patients with αIIb-dependent antibodies. Ten of 14 bound to αIIb (L1-Q459)vβ3, showing that autoepitopes were often localized to this region of αIIb. In addition, each of the autoantibodies binding to αIIb (L1-Q459)vβ3, also bound to CHO cells expressing either αIIb(L1-F223)vβ3 or αIIb(F223-Q459)vβ3). In two of the three eluates tested, > 95% of the autoantibody binding to αIIb could be adsorbed using CHO cells expressing any of the three chimaeras, showing that the epitope(s) have contact points on either side of amino acid F223; in the third eluate, only a portion (∼40%) could be adsorbed by the chimaeric cell lines showing that, in this patient, an additional antibody was also present, directed to a site distal to amino acid Q459. The remaining four eluates bound to CHO cells expressing αIIbβ3 but to none of the chimaeras, suggesting that these epitopes are also distal to amino acid Q459. We conclude that the binding of many anti-αIIbβ3 autoantibodies is dependent on the presence of αIIb amino acids L1-Q459.

Original languageEnglish (US)
Pages (from-to)1132-1136
Number of pages5
JournalBritish journal of haematology
Volume118
Issue number4
DOIs
StatePublished - 2002

Keywords

  • Antiplatelet antibody
  • Autoantibody
  • Autoimmune
  • Chronic ITP

ASJC Scopus subject areas

  • Hematology

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