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.
Study design and 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.
Conclusion: 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.
© 2011 American Association of Blood Banks.