Siemaszko Jagoda, Ussowicz Marek, Rybka Blanka, Ryczan-Krawczyk Renata, Kałwak Krzysztof, Bogunia-Kubik Katarzyna
Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Department and Clinic of Paediatric Bone Marrow Transplantation, Oncology and Haematology, Wroclaw Medical University, Wroclaw, Poland.
Front Genet. 2023 Jun 7;14:1186123. doi: 10.3389/fgene.2023.1186123. eCollection 2023.
Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children. One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions ( rs7301582; rs1049174, rs1154831; rs1264457; rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival. The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of rs1264457 polymorphism in patients' *01:01 allele, which was associated with increased risk of CMV infection ( = 0.050), especially in children positive for CMV IgG before transplantation ( = 0.001). Furthermore, the effect of *01:01 allele on CMV infections was more evident in children above the age of 7 years ( = 0.031). Strong tendencies (0.05 < < 0.10) towards association with the risk of acute GvHD were also observed for the or polymorphisms of the recipients. In addition, rs1154831 and rs1063635 might play a protective role as they were not present in any recipient who died after transplantation. In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.
自然杀伤细胞是同种异体造血干细胞移植（HSCT）后最早重建的淋巴细胞亚群。它们的活性受多种受体-配体相互作用调节，包括MICA分子对激活型NKG2D受体的刺激，以及抑制型NKG2A受体与HLA-E的相互作用。在本研究中，研究工作聚焦于选定的NKG2A和NKG2D受体及其配体（HLA-E和MICA分子）多态性对儿童HSCT后移植后并发症发病机制的影响。对来自单个儿科移植中心的100对供体-受体进行了研究。共对六个单核苷酸替换（rs7301582；rs1049174、rs1154831；rs1264457；rs1051792、rs1063635）进行了基因分型，并分析了多态性对急性和慢性移植物抗宿主病（GvHD）、巨细胞病毒（CMV）感染发生率、疾病复发和生存的影响。评估的多态性在患者及其供体之间的分布没有差异。结果显示，患者*01:01等位基因中的rs1264457多态性有显著影响，这与CMV感染风险增加相关（P = 0.050），尤其是在移植前CMV IgG呈阳性的儿童中（P = 0.001）。此外，*01:01等位基因对CMV感染的影响在7岁以上儿童中更为明显（P = 0.031）。对于受体的 或 多态性，也观察到与急性GvHD风险相关的强烈趋势（0.05 < P < 0.10）。此外，rs1154831和rs1063635可能起到保护作用，因为在移植后死亡的任何受体中都未发现它们。总之，越来越多的证据表明，NKG2受体及其配体的基因分型结果可能对儿科同种异体HSCT的结果具有预后价值，但需要对更大规模的供体和移植受体群体进行更广泛的研究来证实这些观察结果。
