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Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases |
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| Authors: | Cedric Ghevaert Angela Rankin Elly Huiskes Leendert Porcelijn Kaija Javela Riitta Kekomaki Tamam Bakchoul Sentot Santoso Sarah Nutland Deborah J Smyth Graham A Smith Simon McBride Nicholas A Watkins Willem H Ouwehand |
| Institution: | From the Department of Haematology, University of Cambridge, the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, and NHS Blood and Transplant, Cambridge, UK;Sanquin Research, Amsterdam, The Netherlands;the Finnish Red Cross Blood Service, Helsinki, Finland;and the Institute for Clinical Immunology, Justus-Liebig University, Giessen, Germany. |
| Abstract: | BACKGROUND: Maternal alloantibodies against the five common human platelet antigen (HPA) systems (HPA-1 to -3, -5, and -15) are found in only 20% of cases referred for fetal and neonatal thrombocytopenia (FMAIT) investigations. The question asked was whether mismatches for the remaining 11 low-frequency HPAs (HPA-4 and -6bw to -17bw) might in part explain the remaining 80% of cases. STUDY DESIGN AND METHODS: A total of 1054 paternal DNA samples from referred FMAIT cases (among which 223 cases where antibodies against a common HPA were found) were genotyped for 11 low-frequency HPAs as well as a recently discovered polymorphism ( ITGA2B -C2320T). The initial genotyping was carried out by TaqMan and potential heterozygotes were confirmed by DNA sequencing. Clinical and serologic data were collected for each case with a heterozygote father. RESULTS: In total, eight heterozygous fathers were identified: four for HPA-6w, one each for HPA-10w and -11w, and two for HPA-12w. Maternal antibodies against the corresponding antigen were identified in four of the eight cases. In two of these cases, antibodies against HPA-1a and HPA-1b were also found. CONCLUSION: It was concluded that the minor alleles of HPA-4 and -6bw to -17bw are exceptionally rare in the Caucasian population and therefore do not explain the large number of FMAIT referrals which test negative for the common HPA antibodies. |
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