title: Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen-7.
abstract: BACKGROUND
  Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30-year-old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6 x 10(9)/L.
  
  
  METHODS
  To elucidate the maternal cause of NAIT in the infant, serologic and genetic studies, including PLT genotyping and sequence-based analysis, were conducted. Additionally, serologic screening for the new PLT antigen was performed.
  
  
  RESULTS
  Serum from the NAIT infant's mother contained antibodies directed against a human PLT antigen (HPA) of the newborn. Using five-cell-lineage flow cytometry, we localized the antigen to a PLT glycoprotein (GP). Subsequent monoclonal antibody immobilization of PLT antigen assay and PLT immunofluorescence inhibition experiments localized the antigen to the GPIIIa subunit of the GPIIb/IIIa complex. GPIIIa localization was confirmed by sequence-based typing studies, which identified a 1297C>T (407proline>serine substitution) mutation on the ninth exon of the GPIIIa gene. This mutation identified the third allele of HPA-7. Anti-Hit(a) reacted with mutated GPIIIa-transfected cells but not with stable transfectants expressing wild-type GPIIIa. Serologic screening for Hit(a) in the Japanese population revealed a phenotypic frequency of approximately 0.0015.
  
  
  CONCLUSIONS
  We identified a new third allele of HPA-7, which is characterized by a 1297C>T mutation in the GPIIIa gene. This 1297C>T allele was found in 0.15% of the Japanese population. An antibody against this antigen could be the cause of severe NAIT.
authors.affiliation: Japanese Red Cross Osaka Blood Center and Yodogawa Christian Hospital, Osaka 536-8505, Japan.
authors.forename: Yangsook
authors.initials: Y
authors.lastname: Koh
authors.forename: Atsuko
authors.initials: A
authors.lastname: Taniue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishii
authors.forename: Nobuki
authors.initials: N
authors.lastname: Matsuyama
authors.forename: Etsuko
authors.initials: E
authors.lastname: Amakishi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Rika A
authors.initials: RA
authors.lastname: Furuta
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukumori
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hirayama
authors.forename: Keiji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagamine
authors.forename: Susumu
authors.initials: S
authors.lastname: Tamai
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D000918:Antibody Specificity / Q000235:genetics; D016824:Antigens, Human Platelet / Q000097:blood / Q000235:genetics*; D044466:Asian People; D005091:Exons; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D039661:Integrin beta3 / Q000097:blood / Q000235:genetics; D007518:Isoantibodies / Q000097:blood* / Q000235:genetics; D007564:Japan; D020125:Mutation, Missense; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000097:blood / Q000235:genetics*
chemical_list: D016824:Antigens, Human Platelet; D039661:Integrin beta3; D007518:Isoantibodies