Probability of allogeneic hematopoietic stem cell transplant failure depending on the recipient's killer immunoglobulin-like receptor genotype

U. Maslikova, E. G. Khamaganova, M. Drokov, I. Y. Urybin, E. Mikhaltsova, L. Kuzmina, E. Parovichnikova
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Abstract

Introduction. Natural killers are the "first line" of antitumor and antiviral protection in the early stages after аllogeneic hematopoietic stem cell transplantation. Quantitative characteristics reach normal values already in the first month after the infusion of blood stem cells to the recipient. Self-tolerance of natural killers is achieved due to many receptors on their surface, but killer immunoglobulin-like receptors play a key role. Their role is to recognize "self" cells and block signals aimed at destroying their own cells. Knowledge of the functional activity of natural killers urged to studying the impact of mismatches between the inhibitory receptor gene and the ligand on the development of allogeneic hematopoietic stem cell transplant failure.The aim of research was to study the probability of the graft failure development in allogeneic hematopoietic stem cell transplantation depending on the recipient's killer immunoglobulin-like receptor genotype.Material and methods. Genotyping of killer-cell immunoglobulin-like receptors in 66 recipients of blood stem cells by the polymerase chain reaction method was performed in the study. Using an online calculator, receptors were classified as "best", "better" and "neutral" depending on the genotype. The end point of the assessment was the development of graft failure in the presence of different genotypes of immunoglobulin-like receptors in the recipient.Results. According to the data obtained, the presence of the “best” and "better" killer-cell immunoglobulin-like receptor genotype in the recipient significantly increased the risks of developing various forms of graft failure.Conclusion. The presence of the KIR2DL3 genotype in a recipient of hematopoietic stem cells significantly (by 3 times) reduces the likelihood of primary graft failure. This result is of great prognostic significance, although at present no ways of influencing it have been developed. The presence of the “best” killer immunoglobulin-like receptors genotype in the recipient increases the likelihood of developing graft failure by more than 3 times compared to the best and neutral genotype (44.4% vs. 13.4%).
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异基因造血干细胞移植失败的概率取决于受体的杀伤免疫球蛋白样受体基因型
介绍。自然杀手是造血干细胞移植后早期抗肿瘤和抗病毒保护的“第一线”。在向受体输注造血干细胞后的第一个月内,数量特征已达到正常值。自然杀手的自我耐受性是由其表面的许多受体实现的,但杀手免疫球蛋白样受体起着关键作用。它们的作用是识别“自我”细胞并阻断旨在破坏自身细胞的信号。了解自然杀手的功能活性,迫切需要研究抑制受体基因与配体错配对异基因造血干细胞移植失败发生的影响。本研究的目的是研究受体杀伤免疫球蛋白样受体基因型对异体造血干细胞移植中移植物衰竭发展的影响。材料和方法。本研究采用聚合酶链反应法对66例造血干细胞受体的杀伤细胞免疫球蛋白样受体进行基因分型。利用在线计算器,受体根据基因型被分为“最佳”、“较好”和“中性”。评估的终点是在受体中存在不同基因型的免疫球蛋白样受体时移植物衰竭的发展。根据获得的数据,受体中“最佳”和“更好”杀手细胞免疫球蛋白样受体基因型的存在显著增加了发生各种形式移植失败的风险。在造血干细胞受体中存在KIR2DL3基因型可显著降低(3倍)原发性移植物失败的可能性。这一结果具有重要的预测意义,尽管目前还没有开发出影响它的方法。与最佳基因型和中性基因型相比,受体中“最佳”杀手免疫球蛋白样受体基因型的存在增加了发生移植物衰竭的可能性3倍以上(44.4%比13.4%)。
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