Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen-7.
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.
Koh
Yangsook
Y
Japanese Red Cross Osaka Blood Center and Yodogawa Christian Hospital, Osaka 536-8505, Japan.
Taniue
Atsuko
A
Ishii
Hiroyuki
H
Matsuyama
Nobuki
N
Amakishi
Etsuko
E
Hayashi
Tomoya
T
Furuta
Rika A
RA
Fukumori
Yasuo
Y
Hirayama
Fumiya
F
Yoshimura
Keiji
K
Nagamine
Tomoko
T
Tamai
Susumu
S
Nakano
Susumu
S
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*
D016824:Antigens, Human Platelet; D039661:Integrin beta3; D007518:Isoantibodies