title: Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1.
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.
authors: 1] Institute of Experimental Cellular Therapy, Essen University Hospital, Essen, Germany [2] Unit of Molecular and Functional Immunogenetics, San Raffaele Scientific Institute, Milan, Italy.
authors: K
authors: K
authors: Fleischhauer
authors: Histocompatibility, Immunogenetics, and Disease Profiling Laboratory, Stanford University Medical School, Stanford, CA, USA.
authors: M A
authors: MA
authors: Fernandez-Viña
authors: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: T
authors: T
authors: Wang
authors: Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA.
authors: M
authors: M
authors: Haagenson
authors: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: M
authors: M
authors: Battiwalla
authors: Immunogentics and Transplantation Lab, University of California San Francisco Medical Center, San Francisco, CA, USA.
authors: L A
authors: LA
authors: Baxter-Lowe
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors: F
authors: F
authors: Ciceri
authors: National Marrow Donor Program, Minneapolis, MN, USA.
authors: J
authors: J
authors: Dehn
authors: Oregon Health and Science University, Portland, OR, USA.
authors: J
authors: J
authors: Gajewski
authors: Pediatric Hematology/Oncology/BMT, All Children's Hospital, St Petersburg, FL, USA.
authors: G A
authors: GA
authors: Hale
authors: Dutch Transplant Foundation, Leiden, The Netherlands.
authors: M B A
authors: MB
authors: Heemskerk
authors: Department of Pathology, University of Chicago Hospitals, Chicago, IL, USA.
authors: S R
authors: SR
authors: Marino
authors: Blood and Marrow Transplant, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: P L
authors: PL
authors: McCarthy
authors: Department of Medicine/Bone Marrow Transplant, Stanford Hospitals and Clinics, Stanford, CA, USA.
authors: D
authors: D
authors: Miklos
authors: Europdonor Foundation, Leiden University Medical Center, Leiden, Netherlands.
authors: M
authors: M
authors: Oudshoorn
authors: Department of Pathology, University of Texas Health Care System, San Antonio, TX, USA.
authors: M S
authors: MS
authors: Pollack
authors: Department of Hemaotology/Oncology, University of Florida, Gainesville, FL, USA.
authors: V
authors: V
authors: Reddy
authors: Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, USA.
authors: D
authors: D
authors: Senitzer
authors: Anthony Nolan Research Institute, London, UK.
authors: B E
authors: BE
authors: Shaw
authors: Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.
authors: E K
authors: EK
authors: Waller
authors: Clinical Transplant Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: S J
authors: SJ
authors: Lee
authors: Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA.
authors: S R
authors: SR
authors: Spellman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D059867:HLA-DP alpha-Chains / Q000276:immunology*; D059868:HLA-DP beta-Chains / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012306:Risk; D019172:Transplantation Conditioning / Q000379:methods*; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen