Department of Intensive Care, Peking University Shenzhen Hospital, Shenzhen, China.
BMC Infect Dis. 2024 Sep 17;24(1):986. doi: 10.1186/s12879-024-09890-0.
The intricate interplay between genetics and immunology often dictates the host's susceptibility to various diseases. This study explored the genetic causal relationship between natural killer (NK) cell-related traits and the risk of infection.
Single-nucleotide polymorphisms (SNPs) significantly associated with NK cell-related traits were selected as instrumental variables to estimate their genetic causal effects on infection. SNPs from a genome-wide association study (GWAS) on NK cell-related traits, including absolute cell counts, median fluorescence intensities reflecting surface antigen levels, and relative cell counts, were used as exposure instruments. Summary-level GWAS statistics of four phenotypes of infection were used as the outcome data. The exposure and outcome data were analyzed via the two-sample Mendelian randomization method.
Each one standard deviation increase in the expression level of human leukocyte antigen (HLA)-DR on HLA-DR NK cells was associated with a lower risk of pneumonia (P < 0.05). An increased HLA-DR NK/CD3 lymphocyte ratio was related to a lower of risk of pneumonia (P < 0.05). Each one standard deviation increase in the absolute count of HLA-DR NK cells was associated with a lower risk of both bacterial pneumonia and pneumonia (P < 0.05). An increased HLA-DR NK/NK ratio was associated with a decreased risk of both pneumonia and bacterial pneumonia (P < 0.05). The results were robust under all sensitivity analyses. No evidence for heterogeneity, pleiotropy, or potential reverse causality was detected. Notably, our analysis did not reveal any significant associations between NK cell-related traits and other phenotypes of infection, including cellulitis, cystitis, and intestinal infection.
HLA-DR NK cells could be a novel immune cell trait associated with a lower risk of bacterial pneumonia or pneumonia.
遗传学和免疫学之间错综复杂的相互作用常常决定了宿主对各种疾病的易感性。本研究探讨了自然杀伤 (NK) 细胞相关特征与感染风险之间的遗传因果关系。
选择与 NK 细胞相关特征显著相关的单核苷酸多态性 (SNP) 作为工具变量，以估计它们对感染的遗传因果效应。来自 NK 细胞相关特征全基因组关联研究 (GWAS) 的 SNP，包括绝对细胞计数、反映表面抗原水平的中荧光强度和相对细胞计数，被用作暴露工具。将四种感染表型的汇总水平 GWAS 统计数据用作结果数据。通过两样本孟德尔随机化方法分析暴露和结果数据。
HLA-DR NK 细胞上 HLA-DR 表达水平每增加一个标准差，肺炎的风险就会降低（P<0.05）。HLA-DR NK/CD3 淋巴细胞比值增加与肺炎风险降低相关（P<0.05）。HLA-DR NK 细胞的绝对计数每增加一个标准差，细菌性肺炎和肺炎的风险都会降低（P<0.05）。HLA-DR NK/NK 比值增加与肺炎和细菌性肺炎的风险降低相关（P<0.05）。所有敏感性分析结果均稳健。未发现异质性、多效性或潜在的反向因果关系的证据。值得注意的是，我们的分析并未发现 NK 细胞相关特征与其他感染表型（包括蜂窝织炎、膀胱炎和肠道感染）之间存在任何显著关联。
HLA-DR NK 细胞可能是一种与细菌性肺炎或肺炎风险降低相关的新型免疫细胞特征。
