AUTHOR=Siemaszko Jagoda , Ussowicz Marek , Rybka Blanka , Ryczan-Krawczyk Renata , Kałwak Krzysztof , Bogunia-Kubik Katarzyna 

TITLE=The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1186123

DOI=10.3389/fgene.2023.1186123

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (<italic>NKG2A</italic> rs7301582; <italic>NKG2D</italic> rs1049174, rs1154831; <italic>HLA-E</italic> rs1264457; <italic>MICA</italic> 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.</p><p><bold>Results:</bold> The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of <italic>HLA-E</italic> rs1264457 polymorphism in patients’ <italic>HLA-E</italic>*01:01 allele, which was associated with increased risk of CMV infection (<italic>p </italic>= 0.050), especially in children positive for CMV IgG before transplantation (<italic>p</italic> = 0.001). Furthermore, the effect of <italic>HLA-E</italic>*01:01 allele on CMV infections was more evident in children above the age of 7 years (<italic>p</italic> = 0.031). Strong tendencies (0.05 &lt; <italic>p</italic> &lt; 0.10) towards association with the risk of acute GvHD were also observed for the <italic>NKG2A</italic> or <italic>MICA</italic> polymorphisms of the recipients. In addition, <italic>NKG2D</italic> rs1154831 <italic>AA</italic> and <italic>MICA</italic> rs1063635 <italic>GG</italic> might play a protective role as they were not present in any recipient who died after transplantation.</p><p><bold>Conclusion:</bold> 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.</p>