Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases.
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.
Ghevaert
Cedric
C
Department of Haematology, University of Cambridge, Cambridge, UK. c.ghevaert@bham.ac.uk
Rankin
Angela
A
Huiskes
Elly
E
Porcelijn
Leendert
L
Javela
Kaija
K
Kekomaki
Riitta
R
Bakchoul
Tamam
T
Santoso
Sentot
S
Nutland
Sarah
S
Smyth
Deborah J
DJ
Smith
Graham A
GA
McBride
Simon
S
Watkins
Nicholas A
NA
Ouwehand
Willem H
WH
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*
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