title: Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge, UK. c.ghevaert@bham.ac.uk
authors.forename: Cedric
authors.initials: C
authors.lastname: Ghevaert
authors.forename: Angela
authors.initials: A
authors.lastname: Rankin
authors.forename: Elly
authors.initials: E
authors.lastname: Huiskes
authors.forename: Leendert
authors.initials: L
authors.lastname: Porcelijn
authors.forename: Kaija
authors.initials: K
authors.lastname: Javela
authors.forename: Riitta
authors.initials: R
authors.lastname: Kekomaki
authors.forename: Tamam
authors.initials: T
authors.lastname: Bakchoul
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Graham A
authors.initials: GA
authors.lastname: Smith
authors.forename: Simon
authors.initials: S
authors.lastname: McBride
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
mesh_terms: D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000235:genetics* / Q000276:immunology*; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000235:genetics* / Q000276:immunology*
chemical_list: C510800:4b alloantigen, human; C055973:5b alloantigen, human; C108543:6b alloantigen, human; C506267:9bw alloantigen, human; D016824:Antigens, Human Platelet; C528405:HPA-8bw antigen, human; D007518:Isoantibodies