Faculty Collaboration Database

High HLA-DP Expression and Graft-versus-Host Disease. N Engl J Med 2015 Aug 13;373(7):599-609

Date

08/13/2015

Pubmed ID

26267621

Pubmed Central ID

PMC4560117

DOI

10.1056/NEJMoa1500140

Scopus ID

2-s2.0-84941622235 (requires institutional sign-in at Scopus site)   217 Citations

Abstract

BACKGROUND: Transplantation 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.

METHODS: We 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).

RESULTS: The 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).

CONCLUSIONS: The 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.).

Author List

Petersdorf EW, Malkki M, O'hUigin C, Carrington M, Gooley T, Haagenson MD, Horowitz MM, Spellman SR, Wang T, Stevenson P

Authors

Mary M. Horowitz MD, MS 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
Female
Genetic Linkage
Genotype
Graft vs Host Disease
HLA-DP beta-Chains
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Proportional Hazards Models
Regulatory Sequences, Nucleic Acid
Unrelated Donors
Young Adult