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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 |
| Affiliation: | 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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