title: New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia.
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).
  
  
  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.
authors: Blood Research Institute and Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee,WI 53226-3548, USA. Julie.Peterson@bcw.edu
authors: Julie A
authors: JA
authors: Peterson
authors: Shannon M
authors: SM
authors: Pechauer
authors: Maria L
authors: ML
authors: Gitter
authors: Adam
authors: A
authors: Kanack
authors: Brian R
authors: BR
authors: Curtis
authors: Jeff
authors: J
authors: Reese
authors: Vasudeva M
authors: VM
authors: Kamath
authors: Janice G
authors: JG
authors: McFarland
authors: Richard H
authors: RH
authors: Aster
mesh_terms: D016824:Antigens, Human Platelet / Q000276:immunology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000209:etiology*
chemical_list: D016824:Antigens, Human Platelet; D010980:Platelet Membrane Glycoproteins