• Effie W Petersdorf, Mari Malkki, Colm O'hUigin, Mary Carrington, Ted Gooley, Michael D Haagenson, Mary M Horowitz, Stephen R Spellman, Tao Wang, and Philip Stevenson.
• From the Division of Clinical Research, Fred Hutchinson Cancer Research Center (E.W.P., M.M., T.G., P.S.), and the Department of Medicine, University of Washington School of Medicine (E.W.P.) - both in Seattle; Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Frederick National Laboratories for Cancer Research, Frederick, MD (C.O., M.C.); Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston (M.C.); Center for International Blood and Marrow Transplant Research, Minneapolis (M.D.H., S.R.S.); and Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee (M.M.H., T.W.).
• N. Engl. J. Med. 2015 Aug 13; 373 (7): 599609599-609.

BackgroundTransplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1-mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient.MethodsWe genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1-matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression).ResultsThe mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P=0.05).ConclusionsThe risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1-mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.).

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