Abstract
Regulating natural killer (NK) cell responses in hematological malignancies largely depend on molecular interactions between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I ligands. The goal of the current study was to examine the key functions of KIR genes, gene combinations of KIR-HLA, and KIR genotypes in genetic predisposition to aplastic anemia (AA). Herein, the genotyping of 16 KIR genes and HLA-A, -B, and -C ligands were performed in 72 AA patients and 150 healthy controls using PCR evaluations with sequence-specific primers using standard assays. According to the obtained results, AA patients had an increased incidence of activating KIR and KIR2DS4 (P = 0.465 × 10−4, Pc = 0.837 × 10−3, OR = 20.81, 95% CI = 2.786–155.5) compared to controls. KIR/HLA class I ligand profile KIR2DS4/C1 (P = 0.350 × 10−4, Pc = 0.630 × 10−3, OR = 8.944, 95% CI = 2.667–29.993) was significantly elevated in AA patients compared to healthy controls. Genotype AA1 (P = 0.003, OR = 2.351, 95% CI = 1.325–4.172) were increased, and AA195 (P = 0.006, OR = 0.060, 95% CI = 0.004–1.023) was decreased among AA cases compared to controls. Our findings indicated that KIR2DS4 may play a role in the pathogenesis of AA. This study revealed the contribution of KIR genes in the etiology of AA cases.
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Acknowledgements
We are grateful to all the volunteers who were willing to participate into this study.
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This research was supported by the Natural Science Foundation of Xi’an Health Commission (20180509YX3SF29).
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J.W., L.S., and L.C. performed the experiments, analyzed the data, and wrote up the results. T.W., M.W., H.X., and Y.L. planned the experiments, analyzed the data, created the figures, and wrote the manuscript. J.Q. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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To conduct the current study, approval was provided by institutional review committees at the Shaanxi Blood Center and the local ethics committee. Furthermore, both healthy individuals (the control group) and AA patients gave their written consent after getting all the necessary information. Consent was given after a thorough explanation, as specified by the Declaration of Helsinki.
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Wang, T., Qi, J., Wang, M. et al. Correlation between human leukocyte antigen ligands and killer cell immunoglobulin-like receptors in aplastic anemia patients from Shaanxi Han. Immunogenetics 75, 445–454 (2023). https://doi.org/10.1007/s00251-023-01316-6
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DOI: https://doi.org/10.1007/s00251-023-01316-6