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SummaryThe interpretation of the role of HLA-DPB1 in unrelated haematopoietic stem cell transplantation (HSCT) is subject to discussion. We have investigated the role of HLA-DPB1 allele matching in HSCT outcomes in 161 recipients who were HLA-A, -B, -C, -DRB1 and -DQB1-matched with their unrelated donors at the allelic level (10/10). In addition, we analysed the association of polymorphic amino acid mismatches of DPB1 molecule with HSCT end-points, and a previously published permissiveness concept. HLA-DPB1 allele mismatches were significantly associated with an increased incidence of acute graft-versus-host disease (aGvHD) and worse overall survival (OS). The mismatch at amino acid position 69 significantly increased the risk for transplant-related mortality (TRM). Risk factors for aGvHD also included mismatches at positions 8, 9, 35, 76 and 84. This is to our knowledge, the first report of an in vivo effect of single amino acid mismatches on HSCT outcomes. In this study, grouping of allelic mismatches into permissive and non-permissive categories and their association with transplantation end-points was relevant for TRM but not for other clinical end-points.

Interactions of polymorphic killer Ig-like receptor (KIR) receptors with KIR ligands have been shown to modify the outcome of hematopoietic SCT (HSCT). The association of these genetic factors with different transplantation endpoints, however, varies substantially, depending on clinical and study setup variables. We aimed to assess whether KIR ligands, KIR genes and KIR haplotypes are associated with HSCT outcome of 124 patients with various hematological malignancies, transplanted with 12/ 12 HLA matched grafts from unrelated donors. For this purpose, patient and donor KIR gene and KIR ligand polymorphisms were determined and correlated with clinical data in simple and multiple models. We found that a missing HLA-C2 ligand for donor inhibitory KIR2DL1 was significantly associated with an increased risk of acute GVHD (aGVHD) (II-IV) (hazard ratio (HR) ¼ 2.23, 95% confidence interval (95% CI): 1.21-4.10, P ¼ 0.010), as were the AA KIR haplotypes in patients and donors in HLA-C1CX (HR ¼ 2.37, 95% CI: 1.16-4.84, P ¼ 0.018) and in HLA-Bw4 À (HR ¼ 3.20, 95% CI: 1.35-7.60, P ¼ 0.008) patients. On the contrary, transplantation of HLA-C1C2 patients with KIR2DS2 positive grafts were associated with a decreased risk of aGVHD (II-IV) (HR ¼ 0.24, 95% CI: 0.07-0.85, P ¼ 0.027). Thus, our single center study provides evidence for the modification of aGVHD risk by KIRs and their ligands.

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