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 histocompatibility 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 recipient 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 mismatched recipients experienced a significantly increased risk of acute GVHD compared with HLA-DP-identical transplants. Patients who were mismatched for a single HLA-DPB1 allele had an odds ratio (OR) of 1·0 (0·5, 2·2; P = 0·99) and 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-allele 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 the alloimmune response. A threshold effect of multiple HLA-DP disparities is evident in determining the risk of acute GVHD after haematopoietic cell transplantation from unrelated donors.