Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ibα involved in platelet transfusion refractoriness

Mitsuru Murata, Kenichi Furihata, Fumihiro Ishida, Susan R. Russell, Jerry Ware, Zaverio M. Ruggeri

Research output: Contribution to journalArticle

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Abstract

The platelet-specific alloantigen, Siba, located within the α-subunit of the glycoprotein (GP) Ib-IX membrane receptor, has been found to be involved in the pathogenesis of platelet transfusion refractoriness. We have identified the existence of a naturally occurring threonine/methionine dimorphism at position 145 of the GPIbα sequence, and determined that the Siba antigen corresponds to the molecule containing methi-onine145. The diallelic codons can be detected by restriction enzyme analysis of amplified genomic DNA fragments from the GPlbα gene. Evaluation of 61 healthy blood donors showed that the allele frequencies are 89% and 11% for the threonine145 and methionine145 codons, respectively. A positive correlation exists between platelet reactivity with the anti-Siba antibody and the presence of a methionine145-encoding allele. Moreover, recombinant expression of two soluble GPlba fragments differing only at residue 145, provided definitive evidence that the human anti-Siba antibody reacts only with the molecule containing methionine145. These results explain the structural basis of the Siba human alloantigen system and define screening methodologies useful in transfusion medicine to match donor and recipient platelets accordingly.

Original languageEnglish
Pages (from-to)3086-3090
Number of pages5
JournalBlood
Volume79
Issue number11
Publication statusPublished - 1992 Jun 1
Externally publishedYes

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Platelet Glycoprotein GPIb-IX Complex
Platelet Transfusion
Platelets
Codon
Anti-Idiotypic Antibodies
Blood Platelets
Human Platelet Antigens
Transfusion Medicine
Amino Acids
Restriction Mapping
Isoantigens
Threonine
Blood Donors
Gene Frequency
Methionine
Alleles
Tissue Donors
Antigens
Molecules
Membranes

ASJC Scopus subject areas

  • Hematology

Cite this

Murata, M., Furihata, K., Ishida, F., Russell, S. R., Ware, J., & Ruggeri, Z. M. (1992). Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ibα involved in platelet transfusion refractoriness. Blood, 79(11), 3086-3090.

Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ibα involved in platelet transfusion refractoriness. / Murata, Mitsuru; Furihata, Kenichi; Ishida, Fumihiro; Russell, Susan R.; Ware, Jerry; Ruggeri, Zaverio M.

In: Blood, Vol. 79, No. 11, 01.06.1992, p. 3086-3090.

Research output: Contribution to journalArticle

Murata, M, Furihata, K, Ishida, F, Russell, SR, Ware, J & Ruggeri, ZM 1992, 'Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ibα involved in platelet transfusion refractoriness', Blood, vol. 79, no. 11, pp. 3086-3090.
Murata, Mitsuru ; Furihata, Kenichi ; Ishida, Fumihiro ; Russell, Susan R. ; Ware, Jerry ; Ruggeri, Zaverio M. / Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ibα involved in platelet transfusion refractoriness. In: Blood. 1992 ; Vol. 79, No. 11. pp. 3086-3090.
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