학술논문

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.
Document Type
Article
Source
Scandinavian Journal of Immunology. Jul2020, Vol. 92 Issue 1, p1-12. 12p.
Subject
*ALLELES
*HAPLOTYPES
Language
ISSN
0300-9475
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 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. [ABSTRACT FROM AUTHOR]