Faculty Collaboration Database

Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1. Bone Marrow Transplant 2014 Sep;49(9):1176-83

Date

06/24/2014

Pubmed ID

24955785

Pubmed Central ID

PMC4154997

DOI

10.1038/bmt.2014.122

Scopus ID

2-s2.0-85027943464 (requires institutional sign-in at Scopus site)   28 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.

Author List

Fleischhauer K, Fernandez-Viña MA, Wang T, Haagenson M, Battiwalla M, Baxter-Lowe LA, Ciceri F, Dehn J, Gajewski J, Hale GA, Heemskerk MB, Marino SR, McCarthy PL, Miklos D, Oudshoorn M, Pollack MS, Reddy V, Senitzer D, Shaw BE, Waller EK, Lee SJ, Spellman SR

Authors

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Child
Child, Preschool
Cohort Studies
Epitope Mapping
Epitopes, T-Lymphocyte
Female
HLA-DP alpha-Chains
HLA-DP beta-Chains
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Middle Aged
Risk
Transplantation Conditioning
Unrelated Donors
Young Adult