Department of Neurology and Psychiatry, Longyou People's Hospital Affiliated with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Quzhou, Zhejiang, China.
Department of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Front Immunol. 2024 Sep 9;15:1456663. doi: 10.3389/fimmu.2024.1456663. eCollection 2024.
Evidence from observational studies indicates that inflammatory proteins play a vital role in Guillain-Barre Syndrome (GBS). Nevertheless, it is unclear how circulating inflammatory proteins are causally associated with GBS. Herein, we conducted a two-sample Mendelian randomization (MR) analysis to systematically explore the causal links of genetically determined systemic inflammatory proteins on GBS.
A total of 8,293 participants of European ancestry were included in a genome-wide association study of 41 inflammatory proteins as instrumental variables. Five MR approaches, encompassing inverse-variance weighted, weighted median, MR-Egger, simple model, and weighted model were employed to explore the causal links between inflammatory proteins and GBS. MR-Egger regression was utilized to explore the pleiotropy. Cochran's Q statistic was implemented to quantify the heterogeneity. Furthermore, we performed single-cell RNA sequencing analysis and predicted potential drug targets through molecular docking technology.
By applying MR analysis, four inflammatory proteins causally associated with GBS were identified, encompassing IFN-γ (OR:1.96, 95%CI: 1.02-3.78, P=0.045), IL-7 (OR:1.86, 95%CI: 1.07-3.23, P=0.029), SCGF-β (OR:1.56, 95%CI: 1.11-2.19, P=0.011), and Eotaxin (OR:1.99, 95%CI: 1.01-3.90, P=0.046). The sensitivity analysis revealed no evidence of pleiotropy or heterogeneity. Additionally, significant genes were found through single-cell RNA sequencing analysis and several anti-inflammatory or neuroprotective small molecular compounds were identified by utilizing molecular docking technology.
Our MR analysis suggested that IFN-γ, IL-7, SCGF-β, and Eotaxin were causally linked to the occurrence and development of GBS. These findings elucidated potential causal associations and highlighted the significance of these inflammatory proteins in the pathogenesis and prospective therapeutic targets for GBS.
来自观察性研究的证据表明，炎症蛋白在吉兰-巴雷综合征（GBS）中起着至关重要的作用。然而，目前尚不清楚循环炎症蛋白与 GBS 之间是如何存在因果关系的。在此，我们进行了两样本孟德尔随机化（MR）分析，以系统地探讨遗传决定的系统性炎症蛋白与 GBS 之间的因果关系。
我们将欧洲血统的 8293 名参与者纳入了一项针对 41 种炎症蛋白的全基因组关联研究，这些蛋白作为工具变量。我们采用了五种 MR 方法，包括逆方差加权法、加权中位数法、MR-Egger 法、简单模型法和加权模型法，以探讨炎症蛋白与 GBS 之间的因果关系。我们使用 MR-Egger 回归来探讨潜在的偏倚。我们还使用 Cochran's Q 统计量来量化异质性。此外，我们进行了单细胞 RNA 测序分析，并通过分子对接技术预测了潜在的药物靶点。
通过 MR 分析，我们确定了与 GBS 有因果关系的四种炎症蛋白，包括 IFN-γ（OR：1.96，95%CI：1.02-3.78，P=0.045）、IL-7（OR：1.86，95%CI：1.07-3.23，P=0.029）、SCGF-β（OR：1.56，95%CI：1.11-2.19，P=0.011）和 Eotaxin（OR：1.99，95%CI：1.01-3.90，P=0.046）。敏感性分析未发现存在偏倚或异质性的证据。此外，通过单细胞 RNA 测序分析发现了显著的基因，并且通过分子对接技术鉴定了几种具有抗炎或神经保护作用的小分子化合物。
我们的 MR 分析表明，IFN-γ、IL-7、SCGF-β 和 Eotaxin 与 GBS 的发生和发展存在因果关系。这些发现阐明了潜在的因果关系，并强调了这些炎症蛋白在 GBS 发病机制和潜在治疗靶点中的重要性。
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