title: New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Blood Research Institute and Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, Wisconsin 53201-2178, USA. julie.peterson@bcw.edu
authors.forename: Julie A
authors.initials: JA
authors.lastname: Peterson
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gitter
authors.forename: Adam
authors.initials: A
authors.lastname: Kanack
authors.forename: Brian
authors.initials: B
authors.lastname: Curtis
authors.forename: Janice
authors.initials: J
authors.lastname: McFarland
authors.forename: Daniel
authors.initials: D
authors.lastname: Bougie
authors.forename: Richard
authors.initials: R
authors.lastname: Aster
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007231:Infant, Newborn; D039421:Integrin alpha2 / Q000235:genetics* / Q000276:immunology; D039661:Integrin beta3 / Q000235:genetics* / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D008431:Maternal-Fetal Exchange; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000276:immunology; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000235:genetics* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; D000939:Epitopes; C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D007074:Immunoglobulin G; D039421:Integrin alpha2; D039661:Integrin beta3; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins