NCR1 and NCR3 Expression and Genetic Polymorphism are Associated with CMV Infection after Allogeneic Haematopoietic Stem Cell Transplantation
Sylwia Biały, Piotr Łacina, Jagoda Siemaszko, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W. Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-KubikAbstract
Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality due to the compromised immune system after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are pivotal in the immune response following HSCT, as these cells regenerate early and play a crucial role in detecting and eliminating infections. In the present study, we analyzed expression and single nucleotide polymorphisms (SNPs) of genes coding for NK cell Natural Cytotoxicity Receptors (NCRs). Expression was studied on the mRNA level and on the protein level, using flow cytometry to examine NCR-positive NK cell populations. Our study revealed significant higher expression of NCR1 and NCR3 in HSCT recipients with CMV infection compared to those without complications. Additionally, expression of both receptors correlated with expression of IFN-γ. Changes over time after HSCT were observed in the proportion of NCR1+ NK cells. SNPs genotyping identified associations of NCR1 rs1433097 and NCR3 rs11575836 genotypes with increased risk of CMV infection, as well as of NCR3 rs11575836 with post-HSCT overall survival. These results underscore the crucial role of NCRs in the prevention of infection and the development of post-HSCT complications, highlighting their potential as therapeutic targets to improve transplant outcomes.