The biological significance of HLA-DP gene variation in haematopoietic cell transplantation

Although it has been over 25 years since HLA-DP was mapped to the major his tocompatibility complex (MHC), its biological functions remain ill-defined. We sought to test the hypothesis that HLA-DP functions in a manner similar to that of other class II genes by measuring the risk of clinically severe grades III-IV acute graft-vs.-host disease (GVHD) associated with recipien t HLA-DP disparity after haematopoietic cell transplantation. HLA-DPB1 exon 2 was sequenced in 205 patients who underwent transplantation from HLA-A, -B, -C, -DRB1 and -DQB1 allele-matched unrelated donors. HLA-DPB1 mismatche d recipients experienced a significantly increased risk of acute GVHD compa red with HLA-DP-identical transplants. Patients who were mismatched for a s ingle HLA-DPB1 allele had an odds ratio (OR) of 1.0 (0.5, 2.2; P = 0.99) an d patients who were mismatched for two alleles had an OR of 2.2 (1.0, 4.9; P = 0.06) for developing acute GVHD. Compared with matched and single-allel e mismatched transplants, patients who were mismatched for two DPB1 alleles had an OR of 2.2 (1.2, 4.1; P = 0.01). HLA-DP plays an important role in t he alloimmune response. A threshold effect of multiple HLA-DP disparities i s evident in determining the risk of acute GVHD after haematopoietic cell t ransplantation from unrelated donors.