Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1

K. Fleischhauer, M. A. Fernandez-Viña, T. Wang, M. Haagenson, M. Battiwalla, L. A. Baxter-Lowe, F. Ciceri, J. Dehn, J. Gajewski, G. A. Hale, M. B A Heemskerk, S. R. Marino, P. L. McCarthy, D. Miklos, M. Oudshoorn, M. S. Pollack, V. Reddy, D. Senitzer, B. E. Shaw, E. K. WallerS. J. Lee, S. R. Spellman

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1176-1183
Number of pages8
JournalBone Marrow Transplantation
Volume49
Issue number9
DOIs
StatePublished - Sep 1 2014

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1'. Together they form a unique fingerprint.

Cite this