■椎间盘退变(IVDD)是慢性下腰痛的主要原因,每年影响数百万人。目前关于椎间盘退变的研究越来越重视免疫系统在这一过程中的作用。然而,免疫力与椎间盘退变之间的确切关系仍有待完全阐明。
■我们从最新的汇总级GWAS获得了免疫细胞的GWAS数据,包括来自撒丁岛的6,620人和来自五个全球人口的746,667人。IVDD的摘要结果来自FinnGen财团,包括20,001例病例和164,682例对照。我们进行了全面的单变量孟德尔随机化(MR)分析,以探索免疫细胞与IVDD之间的潜在因果关系。使用逆方差加权(IVW)进行初步估计。为了确保鲁棒性,我们采用了额外的MR方法,如MR-Egger,加权中位数,加权模式,和简单的模式。采用各种测试来评估多效性和异质性,包括CochranQ测试,漏检,MR-Egger截距分析和MR-PRESSO检验。为了解释免疫细胞中潜在的混杂因素,我们进行了多变量MR分析.最后,我们通过双向MR研究了免疫细胞与IVDD之间反向关联的可能性.
■总共,我们的研究通过单变量MR鉴定了15个与IVDD显著相关的免疫细胞。其中,9种免疫细胞类型被认为是IVDD的潜在贡献者,而6人被发现有保护作用。重要的是,我们没有观察到异质性或多效性的证据,这标志着我们结果的稳健性。为了减轻免疫细胞之间的混杂,我们利用多变量MR,导致发现只有9种免疫细胞类型对IVDD产生独立影响。这些包括7个危险因素和2个保护因素。此外,我们的分析显示CD39+CD4+T细胞%CD4+T细胞与IVDD之间存在双向因果关系.
■我们的研究结果表明,免疫细胞与IVDD风险之间存在联系,阐明调节IVDD个体免疫细胞功能的潜在治疗途径。然而,具体的潜在机制值得在未来的实验中进一步研究。
Intervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated.
We obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR.
In total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD.
Our findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.