The prevalence of HPA-1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR-DQ haplotypes
(2020) In Scandinavian Journal of Immunology 92(1).- Abstract
Alloimmunization against human platelet antigen (HPA)-1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA-1a alloimmunization is associated with DRB3*01:01, which is associated with several DR-DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA-1a alloimmunization. HPA-1a–alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR-DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA-1a–immunized women compared to 27% in the general population. In the first... (More)
Alloimmunization against human platelet antigen (HPA)-1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA-1a alloimmunization is associated with DRB3*01:01, which is associated with several DR-DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA-1a alloimmunization. HPA-1a–alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR-DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA-1a–immunized women compared to 27% in the general population. In the first population, the DR3-DQ2 haplotype was overrepresented (P <.003). The prevalence of HPA-1a alloimmunization was estimated to be about twice as frequent with DR3-DQ2 compared to DR13-DQ6, together accounting for about 90% of DRB3*01:01–positive individuals. Further, we examined DQB1*02 and DRB4*01:01 alleles for their reported association with HPA-1a alloimmunization, in the context of DR-DQ haplotypes. Since ~ 80% of DQB1*02 alleles are linked to the DR3-DQ2 haplotype, the association might be coincidental. However, the DQB1*02:02–associated DR7-DQ2 haplotype was also overrepresented in alloimmunized women, suggesting a role for this allele or haplotype in HPA-1a alloimmunization. As DRB4*01:01 is predominantly associated with the DR7-DQ2 haplotype in HPA-1a–alloimmunized individuals, the reported association with FNAIT may be coincidental. Typing for DR-DQ haplotypes revealed important genetic associations with HPA-1a alloimmunization not evident from typing individual alleles, and the presence of different DRB3-associated DR-DQ haplotypes showed different prevalence of HPA-1a alloimmunization.
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- author
- Ahlen, Maria Therese ; Heide, Gøril ; Husebekk, Anne ; Skogen, Bjørn ; Kjeldsen-Kragh, Jens LU and Stuge, Tor B.
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alloimmune, DR-DQ haplotype, FNAIT, HLA, human platelet antigen, NAIT
- in
- Scandinavian Journal of Immunology
- volume
- 92
- issue
- 1
- article number
- e12890
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85084855562
- pmid:32299122
- ISSN
- 0300-9475
- DOI
- 10.1111/sji.12890
- language
- English
- LU publication?
- no
- id
- c68195df-4b3f-42ca-8090-0ad3da5bbbd0
- date added to LUP
- 2020-06-17 12:41:55
- date last changed
- 2024-04-03 09:14:54
@article{c68195df-4b3f-42ca-8090-0ad3da5bbbd0,
abstract = {{<p>Alloimmunization against human platelet antigen (HPA)-1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA-1a alloimmunization is associated with DRB3*01:01, which is associated with several DR-DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA-1a alloimmunization. HPA-1a–alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR-DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA-1a–immunized women compared to 27% in the general population. In the first population, the DR3-DQ2 haplotype was overrepresented (P <.003). The prevalence of HPA-1a alloimmunization was estimated to be about twice as frequent with DR3-DQ2 compared to DR13-DQ6, together accounting for about 90% of DRB3*01:01–positive individuals. Further, we examined DQB1*02 and DRB4*01:01 alleles for their reported association with HPA-1a alloimmunization, in the context of DR-DQ haplotypes. Since ~ 80% of DQB1*02 alleles are linked to the DR3-DQ2 haplotype, the association might be coincidental. However, the DQB1*02:02–associated DR7-DQ2 haplotype was also overrepresented in alloimmunized women, suggesting a role for this allele or haplotype in HPA-1a alloimmunization. As DRB4*01:01 is predominantly associated with the DR7-DQ2 haplotype in HPA-1a–alloimmunized individuals, the reported association with FNAIT may be coincidental. Typing for DR-DQ haplotypes revealed important genetic associations with HPA-1a alloimmunization not evident from typing individual alleles, and the presence of different DRB3-associated DR-DQ haplotypes showed different prevalence of HPA-1a alloimmunization.</p>}},
author = {{Ahlen, Maria Therese and Heide, Gøril and Husebekk, Anne and Skogen, Bjørn and Kjeldsen-Kragh, Jens and Stuge, Tor B.}},
issn = {{0300-9475}},
keywords = {{alloimmune; DR-DQ haplotype; FNAIT; HLA; human platelet antigen; NAIT}},
language = {{eng}},
number = {{1}},
publisher = {{Wiley-Blackwell}},
series = {{Scandinavian Journal of Immunology}},
title = {{The prevalence of HPA-1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR-DQ haplotypes}},
url = {{http://dx.doi.org/10.1111/sji.12890}},
doi = {{10.1111/sji.12890}},
volume = {{92}},
year = {{2020}},
}