Elfishawi Sally M, Mossallam Ghada I, El-Fattah Raafat Abd, El-Haddad Alaa, Kamel Azza M
Bone Marrow Transplantation Laboratory Unit, National Cancer Institute, Cairo University, Egypt.
Bone Marrow Transplantation Laboratory Unit, National Cancer Institute, Cairo University, Egypt.
Hum Immunol. 2017 Nov;78(11-12):684-691. doi: 10.1016/j.humimm.2017.10.004. Epub 2017 Oct 7.
The alloreactivity of natural killer (NK) cell after allogeneic hematopoietic stem cell transplantation (AHSCT) is regulated by the interaction between donor killer immunoglobulin-like receptors (KIRs) and recipient human leukocyte antigen (HLA)-class I molecules. The aim was to identify KIR genes, haplotypes and their HLA-class I ligands and to investigate their association with transplantation outcome. The study included 65 patient/donor pairs who received AHSCT from HLA-matched identical siblings. KIR genotyping was done for donors using reverse sequence specific oligonucleotide probes (rSSO) coupled with luminex technology, while HLA-C genotyping was performed in patients using rSSO strip assay. In multivariate analysis, KIR2DS4 was associated with significant reduced incidence of relapse (p = .002). A trend towards reduced incidence of relapse was also observed with more than two KIR B motifs (p = .09), whereas a significant increased relapse was associated with homozygous HLA-C2 ligand compared to combined C1/C2 and C1/C1 (p = .04). Activating KIR2DS3 was associated with rapid leukocyte engraftment (p = .02). While, KIR 2DL5 was associated with decreased CMV infection (p = .03) and better platelets engraftment (p = .05). KIR genes, haplotypes and HLA-C alleles have an impact on HSCT outcome. Better selection of donors with favorable KIR genotype can improve HLA-matched sibling HSCT outcome especially for AML patients.
异基因造血干细胞移植（AHSCT）后自然杀伤（NK）细胞的同种异体反应性受供体杀伤细胞免疫球蛋白样受体（KIR）与受体人类白细胞抗原（HLA）-I类分子之间相互作用的调节。目的是鉴定KIR基因、单倍型及其HLA-I类配体，并研究它们与移植结果的关联。该研究纳入了65例接受来自HLA匹配的同卵同胞的AHSCT的患者/供体对。使用与Luminex技术结合的反向序列特异性寡核苷酸探针（rSSO）对供体进行KIR基因分型，而使用rSSO条带分析法对患者进行HLA-C基因分型。在多变量分析中，KIR2DS4与复发率显著降低相关（p = 0.002）。观察到具有两个以上KIR B基序时复发率有降低趋势（p = 0.09），而与C1/C2和C1/C1组合相比，纯合HLA-C2配体与复发显著增加相关（p = 0.04）。激活型KIR2DS3与白细胞快速植入相关（p = 0.02）。同时，KIR 2DL5与巨细胞病毒感染减少（p = 0.03）和更好的血小板植入相关（p = 0.05）。KIR基因、单倍型和HLA-C等位基因对造血干细胞移植结果有影响。更好地选择具有有利KIR基因型的供体可以改善HLA匹配的同胞造血干细胞移植结果，尤其是对急性髓系白血病患者。
