Yafteh

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A potential factor influencing hematopoietic stem cells transplantation (HSCT) outcome is the presence of donor-derived alloreactive natural killer (NK) cells. This retrospective analysis studied the impact of NK alloreactivity based on the missing KIR ligand, for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) patients undergoing non-T-cell depleted HLA-identical sibling HSCT. Materials and Methods: A total of 78 patients were studied, including 40 patients with AML and 38 patients with ALL. Nearly, all patients were received a uniform myeloablative conditioning regimen and prophylaxis for GVHD. All were genotyped for KIR genes and HLA ligands by means of polymerase chain reaction-sequence specific primers (PCR-SSP). Results: Missing KIR ligand without HLA-A3/11 had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for AML or ALL. In patients with ALL, however, there was a significant missing KIR ligand with HLA-A3/11 effect on DFS (P=0.04) and OS (P=0.02). Conclusion: These data indicate that the absence of HLA class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcomes in non-T-cell depleted HLA-identical sibling hematopoietic stem-cell transplantation and that the lack of HLA-A3/11 for donor KIR3DL2 can contribute to improved survival for patients with ALL.

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The killer cell immunoglobulin-like receptors (KIR) are a recently discovered family of activating and inhibitory receptors which control natural killer (NK) cell function. KIR exist as a diverse family of receptors that have evolved rapidly by both gene duplication and recombination events. These findings were unexpected for a family of genes involved primarily in the innate immune response. Human leukocyte antigen (HLA) class I molecules serve as ligands for the KIR. Several disease association studies indicate a role for interactions between these loci in infectious diseases, autoimmune/inflammatory disorders, cancer and reproduction. Emerging functional data supports a mechanism based on a continuum of inhibition to activation through various compound KIR-HLA genotypes in diseases. This review summarizes the major features of these genes and discusses how they may be involved in both disease pathogenesis and its amelioration.

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Background : Allogeneic hematopoietic stem cells transplantation (HSCT) is a valuable therapy for refractory acute leukemias, leukemias with a high risk for relapse, myelodysplastic syndromes, and chronic myeloid leukemia. HSCT outcome is dependent on several factors, including the stage of disease, degree of human leukocyte antigen (HLA) identity between donor and recipient, conditioning regimen, and development of graft-versus-host disease (GVHD). Recent studies have indicated that another potential factor influencing transplantation outcome is the presence of donor-derived alloreactive natural killer (NK) cells. NK cell alloreactivity has been defined as a mismatch between the donor and recipient killer immunoglobulin-like receptor (KIR) ligands (ligand-ligand model), or as recipient lacking KIR ligands for donor inhibitory KIR (receptor-ligand model), or as a mismatch between the donor and recipient KIR genes (gene-gene model). The anti-leukemic effects of NK cell alloreactivity include lower rates of relapse, graft failure, and GVHD, ultimately translating into higher overall survival (OS). However, the effects of NK cell alloreactivity on the outcome of HSCT in malignant hematopoietic diseases is a topic of debatable.

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Introduction: Killer-cell Immunoglobulin-like Receptors (KIR) are the members of inhibitory and activating receptors expressed chiefly by the natural killer cells (NK). KIR proteins operate as receptors detecting human leukocyte antigen class Ι molecules (HLA). KIRs and their class Ι HLA ligands contribute in the pathogenesis of many kinds of diseases. The aim of this study was to genotypic analysis of KIR/HLA in the Lur population for the first time. Materials and Methods: In this study, 100 unrelated healthy Lur individuals were KIR and HLA ligand typed by polymerase chain reaction-sequence specific primers genotyping assay. Finally, the frequency of KIR and HLA ligand genes and genotypes, as well as KIR/HLA combinations in the Lur population was compared with the Iranian population. Results: Twenty two KIR genotypes and all of the KIR genes were observed in the Lur population. The most prevalent non-framework genes were KIR2DL1 and KIR2DP1 with the frequency of 98% and KIR3DL1 and KIR2DS4 with the frequency of 96% in the Lur population. AA genotype with the frequency of 29% was the most frequent KIR genotype ever regarded in the Lur population. The number one genotype with the frequency of 35% was the most frequent genotype in the Lur population among HLA ligand genotypes. The most common inhibitory and activating KIR/HLA combinations were KIR2DL2/3+HLA-C1 with the frequency of 75% and KIR2DS2+HLA-C1 with the frequency of 47%, respectively. Discussion and Conclusion: The results illustrate that the frequency of KIR genes and genotypes, HLA ligands and the KIR/HLA combinations has total similar features with the Iranian population, but it is still unique by increasing or decreasing of some frequencies in the Lur population.

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Background: Natural Killer (NK) cells, through mechanisms such as cytotoxicity and cytokine production, are among the first line of defence against infections. The ability of NK cytotoxicity is related to Killer cell immunoglobulin-like receptors (KIR) found on the cell surface. Interaction between KIRs and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected cells. Therefore, in continuation of a preliminary study, the aim of this supplementary study was to investigate the impact of KIR genes, HLA ligand genes, and KIR-HLA combinations on susceptibility to tuberculosis (TB) in Lur population. Materials and Methods: The genomic DNA of 50 patients with TB from Lorestan province was genotyped for sixteen KIR genes and their five major HLA class I ligands by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay. Finally, these results were compared with those of 100 healthy Lur individuals. Results: In this study, the frequency of KIR3DS1 was significantly higher in the control group than the patient group (45% vs. 24%, Pc=0.0204). Also, KIR3DS1+HLA-B Bw4Ile80 combination was more frequent in control individuals compared to TB patients (25% vs. 4%, Pc=0.0034). Conclusion: These findings imply a genetic imbalance between activating and inhibitory KIR genes and KIR-HLA combinations in TB patients of Lur population. Low level of activating KIRs and particularly KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to TB in Lur population. Indeed, these findings confirmed the results of our preliminary study.