Identification of eleven novel HLA alleles by sequence based typing (SBT): A∗02:557, A∗11:01:64, B∗40:299, B∗53:37, C∗01:98 N, C∗02:14:02, C∗04:195, C∗08:110, C∗08:111, DRB1∗03:110, DRB∗13:184

Abstract

Accurate HLA typing and matched donor selection is essential for graft outcome in patients receiving a stem cell transplant. Misidentification of new alleles can result in graft failure or acute graft vs. host disease. This study identifies eleven novel HLA alleles at class I and class II loci. Method Unusual or potentially novel HLA alleles were detected during sequence specific oligonucleotide (SSO) intermediate resolution typing. Characterization of novel alleles was performed by sequence based typing (SBT) using group specific and locus specific primers. Results Eleven novel HLA sequences were identified and characterized in 14 individuals, including HLA-A∗11:01:64 in a patient and a haploidentical sibling, C∗04:195 in a patient and a fully matched sibling, and DRB1∗03:110 in two haploidentical sibling donors. Nine of the eleven novel HLA alleles resulted in an amino acid substitution. The null allele C∗01:98 N resulted in a premature stop codon in exon 2. Six out of the eleven novel alleles have nucleotide/amino acid changes in exon 4 and the rest in exon 2. Table 1 shows the differences of nucleotides and amino acids between these novel alleles and their most homologous allele and the location of the changes. Discussion Identification and characterization of novel HLA alleles is important for the selection of appropriate stem cell transplant donors aimed at improving graft outcome and patient survival. Download : Download full-size image