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The first two cases of neonatal alloimmune thrombocytopenia associated with the low‐frequency platelet antigen HPA‐21bw (Nos) in Japan
Author(s) -
Koh Yangsook,
Ishii Hiroyuki,
Amakishi Etsuko,
Hayashi Tomoya,
Matsuyama Nobuki,
Fukumori Yasuo,
Hirayama Fumiya,
Shimizu Junji,
Nakauchi Shohei,
Kawa Keisei
Publication year - 2012
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2011.03491.x
Subject(s) - neonatal alloimmune thrombocytopenia , allele , serology , antigen , immunology , population , allele frequency , antibody , biology , genetics , medicine , fetus , gene , pregnancy , environmental health
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.