Genetic Variant Ups Risk of Graft-Versus-Host Disease in HSCT
(HealthDay News) — The risk of acute graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation with HLA-DPB1 mismatching is influenced by the HLA-DPB1 rs9277534 expression marker, according to a study published in the Aug. 13 issue of the New England Journal of Medicine.
Effie W. Petersdorf, M.D., from University of Washington in Seattle, and colleagues first genotyped rs9277534 in 3,505 persons to define rs9277534-DPB1 haplotypes. Then, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined among 1,441 recipients of transplants from HLA-A,B,C,DRB1,DQB1-matched unrelated donors with only one HLA-DPB1 mismatch. Quantitative polymerase chain reaction was used to assess HLA-DPB1 expression.
The researchers found that mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. In the case of 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 percent confidence interval, 1.25 to 1.89; P < 0.001). Similarly, the risk of death due to causes other than disease recurrence was also higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.25; 95 percent confidence interval, 1.00 to 1.57; P = 0.05).
"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," the authors write.