HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women
(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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- author
- Kjeldsen-Kragh, Jens LU ; Titze, Thomas L. ; Lie, Benedicte Alexandra ; Vaage, John T. and Kjær, Mette
- organization
- publishing date
- 2019-04-09
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood Advances
- volume
- 3
- issue
- 7
- pages
- 7 pages
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:30923048
- 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
- 2024-09-04 05:46:04
@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}}, doi = {{10.1182/bloodadvances.2019032227}}, volume = {{3}}, year = {{2019}}, }