Faculty Collaboration Database

New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion 2010 Feb;50(2):324-33

Date

10/14/2009

Pubmed ID

19821948

Pubmed Central ID

PMC3568744

DOI

10.1111/j.1537-2995.2009.02438.x

Scopus ID

2-s2.0-75749131072 (requires institutional sign-in at Scopus site)   43 Citations

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.

Author List

Peterson JA, Gitter ML, Kanack A, Curtis B, McFarland J, Bougie D, Aster R

Author

Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Animals
Antibodies, Monoclonal
Antigen-Antibody Reactions
Antigens, Human Platelet
CHO Cells
Cricetinae
Cricetulus
Epitopes
Female
Gene Frequency
Humans
Immunoglobulin G
Infant, Newborn
Integrin alpha2
Integrin beta3
Isoantibodies
Male
Maternal-Fetal Exchange
Models, Molecular
Polymorphism, Genetic
Pregnancy
Recombinant Fusion Proteins
Thrombocytopenia, Neonatal Alloimmune