Genetic variation of the HNA-3a encoding gene
Brigitte K Flesch1, Angelika Reil, Jürgen Bux
1German Red Cross Blood Donation Service West, Bad Kreuznach, Germany. b.flesch@bsdwest.de
Transfusion
|May 14, 2011
Summary
New genetic variations in the choline transporter-like protein 2 gene (CTL2) can affect human neutrophil alloantigen-3a (HNA-3a) antibody binding and genotyping. These findings are crucial for developing improved HNA-3a screening assays.
Area of Science:
- Immunogenetics
- Molecular Biology
- Transfusion Medicine
Background:
- Antibodies to human neutrophil alloantigen-3a (HNA-3a) are implicated in transfusion-related acute lung injury.
- HNA-3a and HNA-3b alloantigens arise from a single nucleotide polymorphism in the choline transporter-like protein 2 (CTL2) gene.
- The study aimed to identify additional polymorphisms affecting HNA-3a/b antigenicity and genotyping.
Purpose of the Study:
- To discover novel polymorphisms within the CTL2 gene.
- To assess the impact of these polymorphisms on HNA-3a antibody binding.
- To evaluate potential interference with HNA-3a/b genotyping methods.
Main Methods:
- CTL2 complementary DNA (cDNA) fragments from 67 donors were sequenced.
- Polymerase chain reaction with sequence-specific primers (PCR-SSP) was employed to genotype for identified single nucleotide polymorphisms (SNPs).
- Granulocyte agglutination tests were performed to assess HNA-3a antibody binding to CTL-2 variants.
Main Results:
- Two novel missense mutations were identified in CTL2: Leu153Phe (537C>T) and Thr301Met (988C>T).
- The Leu153Phe substitution, present in the HNA-3a allele, impaired granulocyte agglutination with four of 14 tested HNA-3a antibodies.
- The Thr301Met variation showed minimal impact on antibody binding.
Conclusions:
- The Leu153Phe exchange can hinder HNA-3a alloantibody binding due to its proximity to the HNA-3a/b defining amino acid.
- PCR-SSP genotyping for HNA-3a may yield inaccurate results in HNA-3ab heterozygous individuals carrying the CTL2-537T variation.
- These discoveries necessitate the development of advanced screening assays for HNA-3a.
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