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Transfusion. 2010 Feb;50(2):324-33. doi: 10.1111/j.1537-2995.2009.02438.x. Epub 2009 Oct 10.

New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia.

Author information

1
Blood Research Institute and Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, Wisconsin 53201-2178, USA. julie.peterson@bcw.edu

Abstract

BACKGROUND:

Recent reports suggest that maternal immunization against low-frequency, platelet (PLT)-specific glycoprotein (GP) polymorphisms is a more common cause of neonatal alloimmune thrombocytopenia (NATP) than previously thought.

STUDY DESIGN AND METHODS:

Serologic and molecular studies were performed on PLTs and DNA from three families in which an infant was born with apparent NATP not attributable to maternal immunization against known PLT-specific alloantigens.

RESULTS:

Antibodies reactive only with paternal PLTs were identified in each mother. In Cases 2 (Kno) and 3 (Nos), but not Case 1 (Sta), antibody recognized paternal GPIIb/IIIa in solid-phase assays. Unique mutations encoding amino acid substitutions in GPIIb (Case 2) or GPIIIa (Cases 1 and 3) were identified in paternal DNA and in DNA from two of the affected infants. Antibody from all three cases recognized recombinant GPIIIa (Case 1 [Sta] and Case 3 [Nos]) and GPIIb (Case 2, Kno) mutated to contain the polymorphisms identified in the respective fathers. None of 100 unselected normal subjects possessed the paternal mutations. Enzyme-linked immunosorbent assay and flow cytometric studies suggested that failure of maternal serum from Case 1 (Sta) to react with paternal GPIIIa in solid-phase assays resulted from use of a monoclonal antibody AP2, for antigen immobilization that competed with the maternal antibody for binding to the Sta epitope.

CONCLUSION:

NATP in the three cases was caused by maternal immunization against previously unreported, low-frequency GP polymorphisms. Maternal immunization against low-frequency PLT-specific alloantigens should be considered in cases of apparent NATP not resolved by conventional serologic and molecular testing.

PMID:
19821948
PMCID:
PMC3568744
DOI:
10.1111/j.1537-2995.2009.02438.x
[Indexed for MEDLINE]
Free PMC Article

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