Exploring the causal relationship between inflammatory cytokines and myasthenia gravis: A two-way Mendelian randomization study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-01 DOI:10.1016/j.cyto.2024.156843

Jing-Yu Li , Yan-Jun Ling , Wen-Hui Bao , Wen-Na Zhang , Xin-Miao Han , Xiao-Chen Zheng , Qi Zhao

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引用次数: 0

Abstract

Background

Based on previous research, it is well-established that myasthenia gravis (MG) is linked to chronic inflammation. However, the exact nature of the relationship between inflammatory factors and the development of MG remains unclear. Consequently, the objective of this study is to explore whether alterations in the levels of inflammatory factors, as influenced by genetic factors, are associated with the occurrence of MG. This will be achieved through a two-sample Mendelian randomization (MR) analysis.

Methods

We conducted a bidirectional Mendelian randomization (MR) study utilizing genetic data from genome-wide association studies (GWAS), encompassing 1873 MG cases and 36,370 individuals of European ancestry as controls. Data on inflammatory cytokines were obtained from GWAS data of 8293, healthy participants. The inverse variance-weighted (IVW) method was primarily employed to investigate the causal relationship between exposure and outcome. Additionally, various sensitivity analysis methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were applied to strengthen the reliability of the results. Through these rigorous approaches, we extensively examined the relationship between inflammatory factors and MG; however, further research is required to establish the specific causal relationship.

Results

After applying Bonferroni correction, the genetic predictions revealed a significant correlation between Monokine induced by gamma interferon (MIG) and MG (OR: 1.09, 95 % CI: 1.04–1.14; P = 0.0006). Furthermore, there were preliminary findings indicating a positive genetic association between Eotaxin and interleukin-2 receptor antagonist (IL-2ra) with MG (OR: 0.81, 95 % CI: 0.66–0.99, P = 0.044; OR: 0.80, 95 % CI: 0.68–0.94, P = 0.008). Reverse MR analysis provided initial evidence of associations between MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra with the development of MG. No indications of pleiotropy or heterogeneity among genetic variants were observed (P > 0.05).

Conclusion

This study uncovers a new connection between inflammatory cytokines and MG, shedding light on potential factors contributing to the development of the disease. Elevated levels of Eotaxin and IL-2ra are associated with a higher risk of MG, while indicating that MIG, MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra may be elevated as a result of MG, Especially MIG. These findings suggest that targeting and regulating specific inflammatory factors could offer promising avenues for the treatment and prevention of MG.

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探讨炎症细胞因子与重症肌无力之间的因果关系：一项双向孟德尔随机研究。

背景：根据以往的研究，重症肌无力（MG）与慢性炎症有关。然而，炎症因子与MG发生之间关系的确切性质尚不清楚。因此，本研究的目的是探讨受遗传因素影响的炎症因子水平的改变是否与MG的发生有关。这将通过双样本孟德尔随机化（MR）分析来实现。方法：我们进行了一项双向孟德尔随机化（MR）研究，利用全基因组关联研究（GWAS）的遗传数据，包括1873例MG病例和36,370名欧洲血统的个体作为对照。炎症因子的数据来自8293名健康参与者的GWAS数据。反方差加权（IVW）方法主要用于调查暴露与结果之间的因果关系。此外，采用MR-Egger、加权中位数、简单模型、加权模型、MR-PRESSO等多种敏感性分析方法来加强结果的可靠性。通过这些严格的方法，我们广泛地研究了炎症因子和MG之间的关系；然而，需要进一步的研究来确定具体的因果关系。结果：应用Bonferroni校正后，遗传预测显示γ干扰素（MIG）诱导的单因子与MG之间存在显著相关性(OR: 1.09, 95% CI: 1.04-1.14；p = 0.0006)。此外，初步发现Eotaxin和白细胞介素-2受体拮抗剂（IL-2ra）与MG存在正相关遗传关系(OR: 0.81, 95% CI: 0.66-0.99, P = 0.044；Or: 0.80, 95% ci: 0.68-0.94, p = 0.008)。反向MR分析提供了MIP1α、GROa、IL-13、TRAIL、IL-2ra和IL-1ra与MG发展之间关联的初步证据。遗传变异之间没有多效性或异质性的迹象（P < 0.05）。结论：本研究揭示了炎症细胞因子与MG之间的新联系，揭示了导致该疾病发展的潜在因素。Eotaxin和IL-2ra水平升高与MG的高风险相关，同时表明MIG、MIP1α、GROa、IL-13、TRAIL、IL-2ra和IL-1ra可能因MG而升高，尤其是MIG。这些发现表明，靶向和调节特定的炎症因子可能为治疗和预防MG提供有希望的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.