A1 Refereed original research article in a scientific journal
Effect of NK cell receptor genetic variation on allogeneic stem cell transplantation outcome and in vitro NK cell cytotoxicity
Authors: Nihtilä, Julia; Penna, Leena; Salmenniemi, Urpu; Itälä-Remes, Maija; Crossland, Rachel E.; Gallardo, David; Bogunia-Kubik, Katarzyna; Lacina, Piotr; Bieniaszewska, Maria; Giebel, Sebastian; Karjalainen, Katariina; Jahan, Farhana; Kerkelä, Erja; Hyvärinen, Kati; Koskela, Satu; Ritari, Jarmo; Partanen, Jukka
Publisher: Springer Science and Business Media LLC
Publication year: 2024
Journal: Scientific Reports
Journal name in source: Scientific Reports
Article number: 26988
Volume: 14
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-024-78619-5
Web address : http://doi.org/10.1038/s41598-024-78619-5
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/470967367
Natural killer (NK) cells recognize and may kill malignant cells via their cell surface receptors. Killer cell immunoglobulin-like receptor (KIR) genotypes of donors have been reported to adjust the risk of relapse after allogeneic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia. To test whether non-KIR NK cell receptors have a similar effect, we screened 1,638 genetic polymorphisms in 21 non-KIR NK cell receptor genes for their associations with relapse and graft-versus-host disease (GVHD) after HSCT in 1,491 HSCT donors (from Finland, the UK, Spain, and Poland), divided into a discovery and replication cohort. Eleven polymorphisms regulating or located in CD226, CD244, FCGR3A, KLRD1, NCR3, and PVRIG were associated with the risks for relapse and GVHD. These associations could not be confirmed in the replication cohort. Blood donor NK cells carrying alleles showing genetic protection for relapse had a higher in vitro NK cell killing activity than non-carriers whereas those with alleles genetically protective for GVHD had lower cytotoxicity, potentially indicating functional effects. Taken together, these results show no robust effects of genetic variation in the tested non-KIR NK cell receptors on the outcome of HSCT.
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Funding information in the publication:
The present study was supported by research grants from the TEKES (currently Business Finland) for the SalWe project (JP), the Academy of Finland (JP), Cancer Foundation Finland (JP and JR; JR and JN, and LP), VTR funding from the Government of Finland to the Blood Service, the Finnish Cultural Foundation (FJ), Orion Research Foundation sr (JN), COST Eurograft ActionCA17138 (K B-K, PL, JN, JP, REC), the National Science Centre (Poland) (grant No. 2018/31/B/NZ2/03065) (K B-K, PL, MB and SG), National Institute of Health Carlos III (ISCIII) (Spain) co-funded by the European Union (grants number PI17/00815 and PI20/01353) (DG), Newcastle Hospitals Charity (REC).
