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.