The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

Abstract

IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the definitive choice for treatment of highrisk hematologic malignancies, even in advanced stages (1,2). There is evidence that allogeneic HLA-matched transplantation for patients with lymphoblastic and myeloblastic leukemia is more effective than autogeneic transplantation, because allo-HSCT may induce the graftversus-leukemia (GVL) effect (3,4). The potential benefit of the GVL effect relies on the elimination of residual malignant cells through immunological antitumor effects, induced by alloreactive T and natural killer (NK) cells, which leads to a lower relapse rate in allo-HSCT patients with hematologic malignancies (3,5,6). Despite all the advantages of allo-HSCT, there are still some complications that limit the success of this important procedure, including the development of graft-versushost disease (GVHD) (7). Alloreactive cells in the graft are widely considered to mediate both the GVL effect and GVHD (8).Acute GVHD, a major source of morbidity in HSCT, is mediated by donor allogeneic cytotoxic T cells against host tissues and leads to the recruitment of other effector cells including NK cells (9,10). The pathophysiology of acute GVHD has been described as a three-phase phenomenon: activation of donor-derived T cells, effector phase through Background/aim: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies. Materials and methods:We studied KIR and HLA genotypes in 115 related donors and recipients (56 patients with AML and 59 patients with ALL) who had received allo-HSCT from HLA-matched sibling donors. We evaluated 17 KIR genes and some alleles, including their ligands, using the PCR-SSP assay.Results: KIR gene frequency results between donors and recipients showed that donors had more activating KIR than their recipients. Chi-square comparison of KIR genotype frequencies in donors versus recipients revealed a significant difference (P < 0.001). We found a survival association between the donor lacking and the recipient having group B KIR haplotypes, although this was not statistically significant. Conclusion:This study suggests that we could exploit NK cell alloreactivity as a part of the optimization of donor selection and potential immunotherapeutic regimens to help facilitate good engraftment and reduce the risk of aGVHD incidence after allo-HSCT.

Advancements in HLA Typing Techniques and Their Impact on Transplantation Medicine

“…Studies suggest that matching KIR genes improves outcomes, as disparities may influence NK cell activity and the posttransplant immune response. This highlights the importance of understanding the interplay between KIR genes and HLA molecules for insights into posttransplant complications [ 110 ]. Incorporating KIR gene matching in donor-recipient selection enhances personalized transplantation strategies.…”