Investigating the Correlation Between HLA-II Gene Polymorphism and RhE Alloimmunization in Pregnant Chinese Women

The Rhesus (Rh) blood group is a significant and complicated biological system in humans. Incompatible transfusion or pregnancy with Rh antigens can lead to the production of alloantibodies, among which the anti-E antibody is prevalent. The relationship between Anti-E antibody and HLA-II gene polymorphism in Chinese pregnant women is worth exploring. Our aim in this study was to verify the correlation between HLA-II gene polymorphisms and RhE alloimmunization in pregnant Chinese women through HLA-II typing and DR-RhE structural prediction. In total, 94 anti-E-negative pregnant women and 103 anti-E-positive pregnant women were enrolled from Southwest China Second Hospital, and HLA-II genotyping was performed using next-generation sequencing. NetMHCpan software was used to predict the binding of E -derived anchoring peptides to HLA-DRB1 molecules. AlphaFold was used to analyze the differences in antigen presentation based on the structure of major histocompatibility complex peptides. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 haplotype showed a significant positive association with anti-E. One E-derived anchoring peptide (219FWPSVNSPL227) was predicted to bind to the HLA-DRB1*09:01 molecule. The interaction between the 60Ser of DR9 and 226pro of RhE comprised one hydrogen bond. This study demonstrated that HLA-II haplotypes are associated with allo-anti-E antibodies in pregnant women from Sichuan Province, China. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 phenotype may enhance the formation of anti-E alloantibodies, and the HLA-DRB1*09:01 molecule may play a key role in alloimmunity.