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. 2022 Sep 29:16:981371.
doi: 10.3389/fnins.2022.981371. eCollection 2022.

VSports注册入口 - Natural killer cells-related immune traits and amyotrophic lateral sclerosis: A Mendelian randomization study

Zhenxiang Gong  1 , Yang Liu  1 , Fengfei Ding  2 , Li Ba  1 , Min Zhang  1
Affiliations

Natural killer cells-related immune traits and amyotrophic lateral sclerosis: A Mendelian randomization study

"VSports app下载" Zhenxiang Gong et al. Front Neurosci. .

Abstract

Background: Observational studies have suggested that peripheral immune disorders are associated with amyotrophic lateral sclerosis (ALS). Previous studies predominantly focused on changes in adaptive immunity. However, emerging evidence showed natural killer (NK) cells, an essential component of innate immunity, were involved in the degeneration of motor neurons. However, the causal relationship between dysregulated NK cells-related immune traits and ALS remains unclear VSports手机版. .

Objective: This study aimed to explore the causal relationship between NK cells-related immune traits and the risk of ALS. V体育安卓版.

Materials and methods: Single nucleotide polymorphisms (SNPs) significantly associated with NK cells-related immune traits were selected as instrumental variables to estimate their causal effects on ALS. SNPs from a genome-wide association study (GWAS) on NK cells-related immune traits were used as exposure instruments, including an absolute NK-cells count, absolute HLA-DR+ NK-cells count, NK cells/lymphocytes, NK cells/CD3- lymphocytes, HLA DR+ NK cells/NK cells, HLA DR+ NK cells/CD3- lymphocytes, and the median fluorescence intensities of CD16-CD56+ on NK cells and HLA-DR+ NK cells. Summary-level GWAS statistics of ALS were used as the outcome data V体育ios版. Exposure and outcome data were analyzed using the two-sample Mendelian randomization (MR) method. .

Results: Each one standard deviation increase in the expression levels of CD16-CD56+ on NK cells and HLA-DR+ NK cells were associated with a lower risk of ALS in both the MR-Egger and inverse variance weighted methods (P < 0. 05). The results proved robust under all sensitivity analyses. Neither instrumental outliers nor heterogeneity were detected. VSports最新版本.

Conclusion: Our results suggest that higher expression levels of CD16-CD56+ on NK cells and HLA-DR+ NK cells are associated with a lower risk of ALS. V体育平台登录.

Keywords: Mendelian randomization (MR); amyotrophic lateral sclerosis (ALS); genome-wide association study (GWAS); innate immunity; natural killer cells. VSports注册入口.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Study design and the flow chart of statistical analysis. Three assumptions of the Mendelian randomization in the current study: assumption 1, the selected genetic variances, as instrumental variables, are associated with the risk factor, that is, natural killer (NK) cells-related immune traits in this case; assumption 2, the selected genetic variances are significantly associated with amyotrophic lateral sclerosis (ALS) through the risk factor only; assumption 3, the selected instrumental variables are not associated other confounding factors (the dashed line and cross symbol indicate no association between selected instrumental variables and confounding factors).
FIGURE 2
FIGURE 2
Summary of the causal effects of NK cells-related immune traits on ALS with mendelian randomization. ALS, amyotrophic lateral sclerosis; SNP, single nucleotide polymorphism; NK, natural killer cells; HLA, human leucocyte antigen; OR, odds ratio; CI, confidence interval.
FIGURE 3
FIGURE 3
Scatterplot of single nucleotide polymorphism (SNP) effects on the expression level of CD16–CD56+ on natural killer (NK) cells versus amyotrophic lateral sclerosis (ALS), with the slope of each line corresponding to the estimated Mendelian randomization effect per method.
FIGURE 4
FIGURE 4
The leave-one-single nucleotide polymorphism (ANP)-out sensitivity analyze for the expression level of CD16–CD56+ on natural killer (NK) cells versus amyotrophic lateral sclerosis (ALS). The Y-axis shows the ID of the SNP to be omitted from analysis and the X-axis represents Mendelian randomization (MR) odds ratios. The red line shows MR estimate including all SNPs.
See this image and copyright information in PMC

References

    1. Abecasis G. R., Auton A., Brooks L. D., DePristo M. A., Durbin R. M., Handsaker R. E., et al. (2012). An integrated map of genetic variation from 1,092 human genomes. Nature 491 56–65. 10.1038/nature11632 - DOI - PMC - PubMed
    1. Abel A. M., Yang C., Thakar M. S., Malarkannan S. (2018). Natural killer cells: development, maturation, and clinical utilization. Front. Immunol. 9:1869. 10.3389/fimmu.2018.01869 - "VSports注册入口" DOI - PMC - PubMed
    1. Beers D. R., Appel S. H. (2019). Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies. Lancet Neurol. 18 211–220. 10.1016/S1474-4422(18)30394-6 - "VSports app下载" DOI - PubMed
    1. Beers D. R., Zhao W., Wang J., Zhang X., Wen S., Neal D., et al. (2017). ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight 2:e89530. 10.1172/jci.insight.89530 - DOI (VSports最新版本) - PMC - PubMed
    1. Brooks B. R. (1994). El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J. Neurol. Sci. 124(Suppl.), 96–107. 10.1016/0022-510x(94)90191-0 - DOI - PubMed