Strategies and technical challenges in allele level Class II typing in 2578 bone marrow transplantation donor–recipient pairs

A combined DPA1∼DPB1 amino acid epitope is the primary unit of selection on the HLA-DP heterodimer

“…A total of 20 out of 3,342 (0.6 %) discrepancies for DPB1 and 9 out of 3,342 (0.26 %) for DPA1 were identified and subsequently resolved. Etiology and resolution of discrepancies for this cohort generally followed the categories reported for a largely overlapping subset of N  = 2,578 donors (Williams et al 2008). …”

“…Sequence-specific oligonucleotide typing assays were performed as previously described (Williams et al 2008) using reagents from the local laboratory, the 11th and 12th international workshops (Bignon and Fernandez-Vina 1997), and commercial vendors (Steiner et al 2000). Sequence-based typing for DPA1 was based on a 1,366-nucleotide PCR product including exons 2 through 4 as described previously (Rozemuller et al 1995).…”

Regarding “Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study”

“…For example, in their Supplementary Table S1, of the 99 pairs originally believed to be 12/12 matched based on matching of the ARDs, 23 were discovered to be mismatched after the third-generation sequencing. This observation is not new; discrepancies observed in the level of matching were noted when donorÀrecipient pairs transplanted through the NMDP were retrospectively typed using methods that are not "ultra-high resolution" [3]. Although DNA sequencing is now the gold standard for matching Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org unrelated donor and recipient pairs, the Mayor et al study does not assess whether the third-generation sequencing platform they used is more accurate than other sequencing strategies in current use.…”