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HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women

Kjeldsen-Kragh, Jens LU ; Titze, Thomas L.; Lie, Benedicte Alexandra; Vaage, John T. and Kjær, Mette (2019) In Blood Advances 3(7). p.945-951
Abstract

HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared... (More)

HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [Pglobal] 5 .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother’s HLA-DRB3*01:01 allele on the platelet count of the newborn (Pglobal 5 .0155). Median (range) neonatal platelet counts were 241 3 109/L (59 3 109/L to 393 3 109/L), 107 3 109/L (4 3 109/L to 387 3 109/L) and 32 3 109/L (4 3 109/L to 352 3 109/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a–immunized women.

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published
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in
Blood Advances
volume
3
issue
7
pages
7 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85068306988
ISSN
2473-9529
DOI
10.1182/bloodadvances.2019032227
language
English
LU publication?
yes
id
9d0fac15-012d-4b7e-8f71-8c41a0893ddc
date added to LUP
2019-07-12 09:56:50
date last changed
2019-08-06 03:24:16
@article{9d0fac15-012d-4b7e-8f71-8c41a0893ddc,
  abstract     = {<p>HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [P<sub>global</sub>] 5 .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother’s HLA-DRB3*01:01 allele on the platelet count of the newborn (P<sub>global</sub> 5 .0155). Median (range) neonatal platelet counts were 241 3 10<sup>9</sup>/L (59 3 10<sup>9</sup>/L to 393 3 10<sup>9</sup>/L), 107 3 10<sup>9</sup>/L (4 3 10<sup>9</sup>/L to 387 3 10<sup>9</sup>/L) and 32 3 10<sup>9</sup>/L (4 3 10<sup>9</sup>/L to 352 3 10<sup>9</sup>/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a–immunized women.</p>},
  author       = {Kjeldsen-Kragh, Jens and Titze, Thomas L. and Lie, Benedicte Alexandra and Vaage, John T. and Kjær, Mette},
  issn         = {2473-9529},
  language     = {eng},
  month        = {04},
  number       = {7},
  pages        = {945--951},
  publisher    = {American Society of Hematology},
  series       = {Blood Advances},
  title        = {HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women},
  url          = {http://dx.doi.org/10.1182/bloodadvances.2019032227},
  volume       = {3},
  year         = {2019},
}