Serological characteristics and molecular tracing of 20 cases with rare A el/B el subtypes in the ABO blood group system
10.3760/cma.j.cn114452-20250306-00136
- VernacularTitle:20例罕见ABO血型系统A el/B el亚型的血清学特点及分子溯源
- Author:
Cunquan KONG
1
;
Yuwan DAI
;
Lu YU
;
Xiaoying ZHU
;
Jingli SHI
;
Xiaoxiao GE
;
Tingting XU
;
Lin CHEN
;
Beizhan YAN
;
Li LI
Author Information
1. 河南省人民医院（郑州大学人民医院）输血科，河南 450003
- Publication Type:Journal Article
- Keywords:
ABO blood-group system;
Glycosyltransferases;
Molecular modeling;
Genotype;
Phenotype
- From:
Chinese Journal of Laboratory Medicine
2025;48(12):1592-1598
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the serological and molecular characteristics of rare A el and B el subtypes in the ABO blood group system, and to explore their genotype-phenotype correlation and the potential clinical significance. Methods:From January 1st, 2021, to January 1st, 2025, 289, 815 samples subjected to ABO blood grouping in Henan Provincial People′s Hospital were selected. Samples demonstrating discrepancies between forward and reverse typing, or consistent typing but with abnormal agglutination degree were included. Those affected by underlying diseases, transplantation, age-related and other interferences were excluded. A total of 169 suspected ABO subgroup samples were identified. Sanger sequencing of exons 1-7 and relevant regulatory regions of the ABO gene was performed. Protein structure modeling and mutation effect analysis for two'el′ subtype glycosyltransferases (GTs) were conducted using SWISS-MODEL and PyMOL.Results:A total of 12 Ael, 6 B el, and 2 AB el subtypes were identified. Serological analysis revealed that all 18 A el/B el samples exhibited O phenotype in forward typing. Among them, A el subtypes showed weaker agglutination in reverse typing with A 1c than with Bc (>2+), while the opposite pattern was observed in B el subtypes. The two AB el samples were typed as A in forward typing, with agglutination ranging from 0-1+with Bc in reverse typing. Genetic analysis indicated that AEL.02 (c.646T>A, p.Phe216Ile) was the predominant allele in A el samples accounting for 7 cases. Also, we found an AEL.02-like variant (lacking c.681G>A), AEL.10 (c.963insC), and carrying a compound variant of c.322C>T (p.Gln108Ter) and c.296C>T (p.Thr99Ile). Among B el samples, BEL.03 (c.502C>T, p.Arg168Trp) accounted for 4 cases, one of which lacked the c.297A>G mutation, and novel mutations such as c.145_146dupCG were detected. Structural simulation demonstrated that AEL.02 and BEL.03 disrupted the hydrogen-bonding network within the active centers of GTA and GTB, respectively, and these mutations probably significantly impaired the structural stability of the corresponding GTs. Additionally, the c.296C>T mutation also markedly affected GTA structural stability. Conclusion:A el/B el subtypes are prone to mis-identify routine blood types. Their molecular mechanisms involved a variety of functional variantions, and integrating molecular detection is crucial for achieving accurate sub-typing and transfusion safety.
