Molecular characterization of variant D antigen expression among 56,445 blood donors in East India

对印度东部 56,445 名献血者中变异型 D 抗原表达的分子特征分析

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Abstract

BACKGROUND: Transfusion of red cells from RhD-positive donors to recipients lacking all or some epitopes of the D antigen can lead to the development of anti-D, potentially resulting in hemolytic transfusion reactions. Over 500 RHD alleles affect the qualitative or quantitative expression of the D antigen. There are huge differences in their prevalence among populations. Despite the distinct genetic diversity across multiple sub-populations in India, the prevalence of RHD alleles in the East Indian region has remained unknown. MATERIAL AND METHODS: Standard hemagglutination tests were performed, along with molecular techniques to determine the nucleotide sequence of the RHD gene. RESULTS: Over 3 years, 56,445 blood donors were tested at the Tata Medical Center, Kolkata by serology. We found 23 samples with D-discrepant test results in immediate spin anti-D technique (0.04%), all of them were C+c+. Variant RHD alleles were identified in 15 samples (15/23, 65.2%). The Indian-type weak D (RHD*01W.150) was the most common variant (30.4%, No.=7), occurring in 1 in 8,063 blood donors in East India versus 1 in 729 blood donors in South India (p<0.001). Other identified variants included RHD*06.03.01 (No.=3), RHD*17.05 (No.=2), RHD*01.EL.37 (No.=2), and RHD*01W.96 (No.=1). The remaining 8 samples (8/23, 34.8%) carried the reference RHD allele (RHD*01.01). DISCUSSION: Our findings reveal a lower prevalence of Indian-type weak D in East India than South India, indicating region-specific genetic diversity. The high incidence of wild-type RHD allele with D-discrepancy in East India suggests a potentially novel molecular mechanism. While RHD*06.03.01 and RHD*17.05 have, the 3 others identified RHD alleles have not been associated with anti-D alloimmunization. We recommend D-negative transfusion for individuals with D-variants that have documented alloimmunization, and advocate to investigate the clinical significance of other D-variant alleles prevalent in East India, such as the Indian-type weak D.

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