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- Title
Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1.
- Authors
Fleischhauer, K; Fernandez-Viña, M A; Wang, T; Haagenson, M; Battiwalla, M; Baxter-Lowe, L A; Ciceri, F; Dehn, J; Gajewski, J; Hale, G A; Heemskerk, M B A; Marino, S R; McCarthy, P L; Miklos, D; Oudshoorn, M; Pollack, M S; Reddy, V; Senitzer, D; Shaw, B E; Waller, E K
- Abstract
HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.
- Subjects
ANTIGENS; HETERODIMERS; ALLELES; LINKAGE disequilibrium; EPITOPES; HUMAN T cells; HEMATOPOIETIC stem cells; HLA histocompatibility antigens
- Publication
Bone Marrow Transplantation, 2014, Vol 49, Issue 9, p1176
- ISSN
0268-3369
- Publication type
Article
- DOI
10.1038/bmt.2014.122