P012 HLA-DP Typing is needed to distinguish hla matched siblings from haploidentical or non-hla matched siblings

Abstract

HLA typing by Next Generation Sequencing (NGS) enables three to four field typing of the HLA-A,-B,-C,-DRB1345,-DQA1,-DQB1,-DPA1 and -DPB1 loci in one step, making it easier to identify potential haematopoietic cell family donors who are HLA matched. This study presents three cases where HLA-DP typing, as part of the standard NGS protocol, distinguished HLA matched siblings from haploidentical or non–haplotype matched siblings. HLA-A,-B,-C,-DRB1345,-DQA1,-DQB1,-DPA1 and -DPB1 typing by NGS was carried out using the Illumina TruSight HLA v2 Sequencing Panel on the Illumina MiSeq instrument, with Assign 2.1 TruSight HLA Analysis software (Illumina, San Diego, CA, USA). The study includes 58 adult patients and 124 siblings; and 10 paediatric patients, both parents and 19 siblings. NGS typing showed 24 (41%) of the adult patients had at least one HLA-A,-B,-C,-DRB1345,-DQA1,-DQB1,-DPA1 and -DPB1 matched sibling, while 43 (74%) had a presumed haploidentical sibling, (no parents were available to confirm haplotypes). In one case, the adult patient and all five siblings were fully matched at HLA-A,-B,-C,-DRB1345,-DQA1 and -DQB1. However, three siblings had different DPB1 alleles to the patient, indicating they were haploidentical, rather than being HLA matched. In another case, two siblings were HLA-A,-B,-C,-DRB1345,-DQA1, and -DQB1 identical to each other, but differed at DPB1. The DP difference meant only one sibling was haploidentical to the adult patient. With the paediatric cases, there was one family where a crossover appeared to have occurred between HLA-DQ and HLA-DP in one of the two healthy siblings, although neither was a haplotype match to the patient. With the implementation of NGS typing, HLA-DPA1 and -DPB1 typing is now routine in our laboratory for all haematopoietic cell transplant workups. This has shown some siblings, who previously would have been thought to be HLA matched (based on HLA-A,-B,-C,-DRB1345,-DQA1 and -DQB1), were only haplotype matched, while other siblings thought to be haplotype matched were not, once HLA-DP typing was considered. Therefore it is beneficial to include HLA-DP typing for all haematopoietic cell transplant workups.