STAFFORD, Prachi, GARNER, Stephen F., RANKIN, Angela, KEKOMAKI, Riitta, WATKINS, Nicholas A. and OUWEHAND, Willem H. (2008). A single-nucleotide polymorphism in the human ITGB3 gene is associated with the platelet-specific alloantigen Va (HPA-17bw) involved in fetal maternal alloimmune thrombocytopenia. Transfusion, 48 (7), 1432-1438.
Full text not available from this repository.Abstract
BACKGROUND - The previously reported platelet (PLT)-specific antigen, Va(a), was defined by an alloantibody detected in the serum sample of a mother who delivered an infant displaying symptoms of severe fetal maternal alloimmune thrombocytopenia (FMAIT). This PLT antigen was localized to the integrin alphaIIbbeta3 (GPIIbIIIa) but its genetic basis was not defined.
STUDY DESIGN AND METHODS - Genomic ITGA2B (alphaIIb) and ITGB3 (beta3) DNA from a Va(a)-positive individual were sequenced to identify potential polymorphisms underlying the Va(a) antigen. Recombinant beta3 integrin carrying the putative mutation was then used to assess serologic reactivity with the original maternal Va(a) antiserum.
RESULTS - A single-nucleotide polymorphism (SNP; C622>T) in exon 5 of ITGB3 resulting in the replacement of threonine with methionine at residue 195 of the mature beta3 was identified. Calmodulin-tagged soluble recombinant beta3 encoding Met195 was produced in S2 cells and found to react specifically with the Va(a) antiserum.
CONCLUSION - With the use of a combination of DNA sequencing and recombinant antigen expression, the molecular basis of the PLT-specific Va(a) antigen (HPA-17bw), a low-frequency antigen implicated in FMAIT, has been resolved. These data further demonstrate the value of using recombinant beta3 peptides for the detection of rare but clinically relevant antibodies.
Item Type: | Article |
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Additional Information: | Article first published online: 15 MAY 2008 |
Research Institute, Centre or Group - Does NOT include content added after October 2018: | Biomedical Research Centre |
Identification Number: | https://doi.org/10.1111/j.1537-2995.2008.01737.x |
Page Range: | 1432-1438 |
Depositing User: | Jamie Young |
Date Deposited: | 03 Jun 2015 13:26 |
Last Modified: | 18 Mar 2021 18:45 |
URI: | https://shura.shu.ac.uk/id/eprint/10000 |
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