Faculty Collaboration Database

New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia. Transfusion 2012 May;52(5):1117-24

Date

11/11/2011

Pubmed ID

22070736

Pubmed Central ID

PMC3564505

DOI

10.1111/j.1537-2995.2011.03428.x

Scopus ID

2-s2.0-84859753456 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

BACKGROUND: Maternal immunization against low-frequency, platelet (PLT)-specific antigens is being recognized with increasing frequency as a cause of neonatal alloimmune thrombocytopenia (NAIT).

STUDY DESIGN AND METHODS: Serologic and molecular studies were performed on PLTs and DNA from two families in which an infant was born with severe thrombocytopenia not attributable to maternal immunization against known PLT-specific alloantigens.

RESULTS: Antibodies reactive only with paternal PLTs were identified in each mother using flow cytometry and solid-phase assays. Unique mutations encoding amino acid substitutions K164T in glycoprotein (GP)IIb (Case 1) and R622W in GPIIIa (Case 2) were identified in paternal DNA and in DNA from the affected infants. Each maternal antibody recognized recombinant GPIIb/IIIa mutated to contain the polymorphisms identified in the corresponding father. None of 100 unselected normal subjects possessed these paternal mutations.

CONCLUSIONS: Severe NAIT observed in the affected infants was caused by maternal immunization against previously unrecognized, low-frequency antigens created by amino acid substitutions in GPIIb/IIIa (α(IIb) /β(3) integrin). A search should be conducted for novel paternal antigens in cases of apparent NAIT not explained on the basis of maternal-fetal incompatibility for known human PLT antigens.

Author List

Peterson JA, Pechauer SM, Gitter ML, Kanack A, Curtis BR, Reese J, Kamath VM, McFarland JG, Aster RH

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

Antigens, Human Platelet
Female
Humans
Infant, Newborn
Male
Mutation
Platelet Membrane Glycoproteins
Polymorphism, Genetic
Pregnancy
Thrombocytopenia, Neonatal Alloimmune