High HLA-DP Expression and Graft-versus-Host Disease

Area of Science:

• Immunogenetics
• Transplantation immunology

Background:

• Hematopoietic cell transplantation offers a cure for blood disorders but poses a risk of acute graft-versus-host disease (GVHD).
• HLA-DPB1 mismatches increase GVHD risk, yet underlying mechanisms remain unclear.
• The rs9277534 variant in the HLA-DPB1 regulatory region affects gene expression.

Purpose of the Study:

• To investigate the association between the rs9277534 allele and GVHD risk in HLA-DPB1 mismatched unrelated donor hematopoietic cell transplants.
• To determine if the expression level of the mismatched HLA-DPB1 allele, influenced by rs9277534, correlates with GVHD incidence.

Main Methods:

• Genotyped rs9277534 in 3505 individuals to establish rs9277534-DPB1 haplotypes.
• Analyzed 1441 recipients with a single HLA-DPB1 mismatch from HLA-A,B,C,DRB1,DQB1-matched unrelated donors.
• Assessed HLA-DPB1 expression and compared GVHD risk between recipients with rs9277534G (high expression) and rs9277534A (low expression) linked to the mismatched HLA-DPB1.

Main Results:

• Mean HLA-DPB1 expression was lower with the rs9277534A allele compared to the rs9277534G allele.
• Recipients with an rs9277534G-linked mismatched HLA-DPB1 had a significantly higher risk of acute GVHD (HR, 1.54; P<0.001).
• A higher risk of non-relapse mortality was also observed in recipients with the rs9277534G-linked mismatch (HR, 1.25; P=0.05).

Conclusions:

• The rs9277534 expression marker influences GVHD risk in HLA-DPB1 mismatched transplants.
• Recipients receiving transplants from donors with a low-expression (rs9277534A-linked) HLA-DPB1 allele, but possessing the high-expression (rs9277534G-linked) allele themselves, faced elevated GVHD risk.