121-P

Abstract

Aim Increased novel allele discovery has a huge contribution to HLA diversity, which could, however, complicate donor search. Currently, no clear guidelines of unrelated hematopoietic stem cell (HSC) donor search are available when novel alleles are involved. Novel alleles raise questions of the clinical significance of the substitution and its effect on unrelated donor search. In this study we present an approach to evaluate a novel allele for donor search. Methods HLA high resolution typing was performed by SBT. We examined the clinical significance of a novel DQB1 ∗ 06:XX allele for the difference between it and the common DQB1 ∗ 06:02, the nature of the changed amino acid, and the location of the changed amino acid on three dimensional structure (α helix or β sheet). Results DQB1 high resolution typing revealed a novel allele identical to DQB1 ∗ 06:02 with except for a mismatch at position 25 within exon 2. The Nucleotide changed from ‘G’ to ‘T’ which caused amino acid changing from Glycine to Valine at codon 13(β13) in the amino-terminal region. The mutation is located on the floor of groove accommodating anchor position pocket 4 (P4). The side group of Glycine in DQB1 ∗ 06:02 changed from –H to –C3H7 for Valine in novel DQB1 ∗ 06:XX. The replaced side group –C3H7 occupies more space and possesses more hydrogen bonds. Although the shape and affinity of the peptide binding pocket might be altered due to changing of the side chain, both Valine and Glycine still belong to hydrophobic amino acid group. High resolution HLA typing of his mother and three siblings were also performed. The novel allele was inherited from the mother. Conclusions Our findings suggest that the amino acid change of the novel allele DQB1 ∗ 06:XX might not be clinically significant based on its location and characteristics when compared to the common DQB1 ∗ 06:02. The method we used to evaluate a novel allele could be a practical approach for the unrelated donor search for a potential HSC recipient with a novel allele of any loci.