A monoclonal antibody (SZ21) specific for platelet GPIIIa distinguishes P1 A1 from Pl A2

E. J. Weiss, P. J. Goldschmidt‐Clermont, D. Grigoryev, Y. Jin, T. S. Kickler, P. F. Bray

Research output: Contribution to journalArticle

Abstract

Abstract: Neonatal alloimmune thrombocytopenia (NATP) and post‐transfusion purpura (PTP) are acquired bleeding disorders caused by alloimmune thrombocytopenia. In most cases, the thrombocytopenia is due to an alloantibody directed against the platelet glycoprotein IIb‐IIIa (GPIIb‐IIIa) complex. During the course of routine studies on the role of GPIIb‐IIIa in inherited and acquired bleeding and thrombotic disorders, we unexpectedly identified an individual whose platelets reacted by non‐reduced Western blot analysis with anti‐GPIIIa polyclonal antisera, but did not react with a commercially available monoclonal antibody (SZ21) specific for GPIIIa. We screened all 14 GPIIIa exons for possible nucleotide changes which might alter amino acids and found variations in only exons 3 and 10. Nucleotide sequencing revealed that only the exon 3 alteration changed the predicted amino acid sequence. This variation was caused by homozygosity for the uncommon PlA2 allele of the GPIIIa gene. Platelets from two additional unrelated normal individuals known to be homozygous for PlA2 also lacked reactivity with SZ21 by Western blot. Using flow cytometry with intact platelets, we observed a markedly reduced binding of SZ21 to platelets with the PlA2 genotype. Scatchard analyses indicated that SZ21 bound to P1A1/A1 platelets with a Kd of 8.26times 10‐10 M, and to P1A2/A2 platelets with a Kd of 5.58times10‐9 M. Thus, we have characterized a readily available monoclonal antibody able to distinguish between the two P1A alleles of the GPIIIa gene. Because incompatibility for this platelet polymorphism is the most common cause of neonatal alloimmune thrombocytopenia and posttransfusion purpura, and because platelet immunophenotyping reagents lack specificity and are not easily available, this monoclonal antibody could facilitate the management of patients with these disorders.

Original languageEnglish (US)
Pages (from-to)374-381
Number of pages8
JournalTissue Antigens
Volume46
Issue number5
DOIs
StatePublished - Nov 1995

Keywords

  • SZ21
  • glycoprotein IIb‐IIIa
  • immunophenotyping
  • monoclonal antibody
  • platelet alloantigen P1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

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