The first two cases of neonatal alloimmune thrombocytopenia associated with the low-frequency platelet antigen HPA-21bw (Nos) in Japan.
BACKGROUND
Neonatal alloimmune thrombocytopenia (NAIT) is a disorder characterized by maternal alloimmunization against paternal fetal platelet antigens. Two healthy, unrelated Japanese women each gave birth to a child with severe NAIT.


METHODS
To elucidate the maternal causes of NAIT, we conducted serologic and genetic studies in these two NAIT infants.


RESULTS
The serologic experiments localized the antigens to the glycoprotein (GP) IIIa subunit of the GPIIb/IIIa complex. Sequence-based typing studies subsequently identified a G>A mutation at Nucleotide 1960 (a glutamic acid > lysine substitution at Position 628) in the 11th exon of the GPIIIa gene. This mutation was recently identified in a report as HPA-21bw. Next, it was determined that the cause of NAIT in both cases was the HPA-21bw antigen, as shown by the mothers' antibodies reacting with the mutated GPIIIa-transfected cells, but not with transfectants expressing wild-type GPIIIa. A molecular genetic screening for the HPA-21bw allele among Japanese donors showed that its genetic frequency in the population was 0.53% (10/1888), indicating that HPA-21bw occurs at a low but appreciable frequency in the population. Furthermore, in a retrospective study of 50 previous NAIT cases of unknown causes, we found one NAIT case associated with the HPA-21bw antibody. The two NAIT cases in this study represent the first ones to be associated with HPA-21bw in Japan.


CONCLUSIONS
We identified the HPA-21bw allele from two unrelated Japanese infants with severe NAIT. We identified 10 individuals (1.06%) positive for the HPA-21bw allele from a genetic screening of 944 Japanese blood donors.
Japanese Red Cross Osaka Blood Center, Osaka, Japan.
Yangsook
Y
Koh
Hiroyuki
H
Ishii
Etsuko
E
Amakishi
Tomoya
T
Hayashi
Nobuki
N
Matsuyama
Yasuo
Y
Fukumori
Fumiya
F
Hirayama
Junji
J
Shimizu
Shohei
S
Nakauchi
Keisei
K
Kawa
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology; D044466:Asian People; D001782:Blood Donors; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D039661:Integrin beta3 / Q000235:genetics*; D007564:Japan; D008297:Male; D009154:Mutation; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000235:genetics* / Q000276:immunology / Q000628:therapy
D016824:Antigens, Human Platelet; D039661:Integrin beta3