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循环细胞因子水平与视神经脊髓炎谱系疾病风险:一项孟德尔随机研究。

The levels of circulating cytokines and risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

机构信息

Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China.

Department of Neurology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.

出版信息

Front Immunol. 2024 Jul 1;15:1418309. doi: 10.3389/fimmu.2024.1418309. eCollection 2024.

Abstract

BACKGROUND

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear.

METHODS

Mendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD.

RESULTS

After Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR): 11.01, 95% confidence interval (CI): 1.16-104.56, = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46-10569.21, = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78-26.93, = 0.006).

CONCLUSION

These findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.

摘要

背景

视神经脊髓炎谱系疾病(NMOSD)是一种影响中枢神经系统(CNS)的炎症性自身免疫性疾病。NMOSD 的发病机制涉及全身炎症。然而,循环细胞因子水平与 NMOSD 之间的因果关系尚不清楚。

方法

采用孟德尔随机化(MR)方法研究了遗传决定的循环 19 种炎症细胞因子和 12 种趋化因子水平与 NMOSD 发病风险之间的潜在关联。

结果

经 Bonferroni 校正后,提示水通道蛋白 4 抗体(AQP4-ab)阳性 NMOSD 的风险与三种细胞因子的循环水平存在因果关系,包括白细胞介素(IL)-4 [比值比(OR):11.01,95%置信区间(CI):1.16-104.56, = 0.037]、IL-24(OR:161.37;95% CI:2.46-10569.21, = 0.017)和 C-C 基序趋化因子 19(CCL19)(OR:6.87,95% CI:1.78-26.93, = 0.006)。

结论

这些发现表明,IL-4、IL-24 和 CCL19 水平升高的遗传易感性可能对 AQP4-ab 阳性 NMOSD 的风险产生因果影响。需要进一步的研究来阐明这些细胞因子如何影响 AQP4-ab 阳性 NMOSD 的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e96/11246864/7c45135b2ea7/fimmu-15-1418309-g001.jpg

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