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

Wenling Shang; Guojin Ou; Xin Ji; Jian Chen; Jue Wang; Yongmei Jiang

doi:10.1007/s12288-023-01632-7

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

Indian J Hematol Blood Transfus. 2023 Oct;39(4):662-669. doi: 10.1007/s12288-023-01632-7. Epub 2023 Feb 1.

Authors

Wenling Shang¹, Guojin Ou^{1

2}, Xin Ji^{3

4}, Jian Chen^{1

2}, Jue Wang^{3

4}, Yongmei Jiang^{1

2}

Affiliations

¹ Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, Ren Min Nan Lu, Chengdu, 610041 Sichuan China.
² Ministry of Education, Key Laboratory of Birth Defects and Related Diseases of Women and Children, (Sichuan University), Chengdu, Sichuan China.
³ Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS and PUMC, No. 26 Hua-Cai Road, Chengdu, 610052 Sichuan China.
⁴ Key Laboratory of Transfusion Adverse Reactions, CAMS and PUMC, Chengdu, Sichuan China.

PMID: 37786831
PMCID: PMC10542046 (available on 2024-10-01)
DOI: 10.1007/s12288-023-01632-7

Abstract

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.

Keywords: Alloimmune antibody; Antibodies; Blood system; Rh factor.

© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.