Identification of the rs9277534 HLA-DP expression marker by next generation sequencing for the selection of unrelated donors for hematopoietic cell transplantation

• Published in: Human immunology 2019-10, Vol.80 (10), p.828-833
• Main Authors: Balgansuren, Gansuvd, Regen, Lois, Sprague, Maggie, Shelton, Nakita, Petersdorf, Effie, Hansen, John A.
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Alleles; Databases, Genetic; Exons - genetics; Genetic Loci - genetics; Genotype; Graft vs Host Disease - genetics; Hematopoietic Stem Cell Transplantation - methods; High-Throughput Nucleotide Sequencing; Histocompatibility Testing; HLA-DP beta-Chains - genetics; HLA-DPB1 expression marker; Humans; NGS; Polymorphism, Single Nucleotide - genetics; SNP rs9277534; Unrelated Donors
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2019.05.010

Mismatching of an unrelated donor against a high-expression HLA-DPB1 recipient allele is associated with a high risk of graft-versus-host disease and mortality. The Seattle Cancer Care Alliance (SCCA) and Fred Hutchinson Cancer Research Center transplant program employs an algorithm to match for HLA-A, B, C, DRB1, DQB1 and DPB1 alleles (12/12) and to avoid, whenever possible, donor mismatching against a recipient high-expression HLA-DPB1 allele. HLA-DPB1 expression is associated with the rs9277534 A/G polymorphism located in the 3′UTR of the HLA-DPB1 gene. Next generation sequencing of HLA-DPB1 using the Illumina TruSight HLA V2 Sequencing Panel and Conexio Assign software analyses provides information on rs9277534 variants without the need for any additional SNP testing. Here we present the molecular location of rs9277534 in NGS data and discuss the challenges to resolve HLA-DPB1 ambiguities.