The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population

Abstract

Background and ObjectivesAnti‐E alloantibody is the most common and important red blood cell (RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA) allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population.Study Design and MethodsAll individuals included in our study were RhE‐negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti‐E (responders) and non‐anti‐E‐producing group (non‐responders). The class I and II classical HLA genotyping were determined using next‐generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non‐responders.ResultsIn total, 76 responders and 94 non‐responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 phenotypes than non‐responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA‐DRB1*09:01‐DQA1*03:02‐DQB1*03:03 in the RhE responders was significantly higher than in the non‐responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823–5.456; pc value, 1.25 × 10−3).ConclusionOur findings indicated that HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three‐locus haplotype in the RhE responders and collaborated to RhE alloimmunization.