Selection of DPB1 T-Cell Epitope Permissive Matching Likely for Patients with 10/10 Unrelated Donors

Recent research suggests that beyond 8/8 allele level matching at HLA-A, B, C, DRB1, matching at HLA-DPB1 should be considered to improve patient survival rates in allogeneic stem cell transplantation.   DPB1 alleles have been separated into three T-cell epitope (TCE) groups based on reactivity in functional assays for matching: 1) high 2) intermediate 3) low immunogenic potential.  Non-permissive TCE mismatches at DPB1 are associated with a higher incidence of transplant related mortality in patients that have a 10/10 matched donor. 

We performed a study to identify the likelihood of having a DPB1 permissive TCE matched donor for patients with 10/10 high resolution matched donor options (HapLogic^® prediction of ≥75%) in the Be The Match Registry^®.  163 patient searches from US transplant centers that submitted a preliminary search request with DPB1 typing were evaluated for DPB1 TCE permissive mismatched donors, either identified through existing registry typing or by prospectively typing up to 10 donors per patient.   

88 of 163 patient searches had a DPB1 TCE permissive mismatch present on the initial search results, 11 patient searches did not have a potential DPB1 matched donor, and the remaining 64 patient searches had up to 10 donors per patient selected for DPB1 typing, prioritizing young male donors.  57 out of 64 patients were able to find a DPB1 TCE permissive match via donor typing resulting in an overall TCE permissive match rate of 89%.  Table 1 shows the condensed TCE groups of the patients assessed in the study, with patients being classified by their highest immunogenic TCE reactivity (i.e. 1>2>3).  On initial donor search results, patients carrying any DPB1 TCE group 1 allele found a match 18% of the time, 34% for group 2 and 63% for group 3.  Typing donors significantly improved the identification of a DPB1 permissive mismatched donor for all 3 groups to 55% for TCE group 1, 71% group 2 and 97% for group 3. 

This study selection process focused on patients with more productive searches and shows that identifying a DPB1 TCE permissive matched donor in these cases is likely for the majority of patients.  HLA typing donors who are predicted to be 10/10 matches for HLA-DPB1 may provide a feasible strategy for optimizing donor selection regardless of patient TCE group.

Table 1: Combined TCE Group of Patient and Likelihood of Identifying a DPB1 allele/permissive mismatched donor.

Patient TCE Group	Pre-Typing TCE Match (%)	Post-Typing TCE Match (%)	Total
Group 1	2 (18%)	6 (55%)	11
Group 2	12 (34%)	25 (71%)	35
Group 3	74 (63%)	114 (97%)	117
Total	88 (54%)	145 (89%)	163