Circulating Interleukins and Risk of Multiple Sclerosis: A Mendelian Randomization Study
Hui Lu1, Peng-Fei Wu2,3, Wan Zhang3,4
1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Frontiers in Immunology
|May 3, 2021
Summary
This study found that higher levels of interleukin-2 receptor alpha (IL-2Rα) are causally linked to an increased risk of developing Multiple Sclerosis (MS). This research clarifies the role of inflammation in MS pathogenesis.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Systemic inflammation is implicated in Multiple Sclerosis (MS) development.
- The precise causal links between specific interleukins (ILs) and MS risk remain unclear.
- Understanding these relationships is crucial for developing targeted MS therapies.
Purpose of the Study:
- To investigate the causal associations between genetically determined circulating levels of various interleukins (ILs) and the risk of Multiple Sclerosis (MS).
- To apply Mendelian randomization (MR) approaches for robust causal inference.
- To elucidate the role of specific ILs in MS pathogenesis.
Main Methods:
- Utilized Mendelian randomization (MR) with genetic instruments for IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18.
- Obtained summary-level data from large-scale genome-wide association studies (GWAS) and the International Multiple Sclerosis Genetics Consortium.
- Performed MR analyses using R software and the TwoSampleMR package.
Main Results:
- Elevated circulating levels of IL-2 receptor α subunit (IL-2Rα) showed a significant causal association with increased MS risk (OR 1.22, p < 0.001).
- A suggestive inverse association was observed for IL-1 receptor antagonist (IL-1Ra) with MS risk (OR 0.94, p = 0.027).
- No significant causal associations were found for IL-6, IL-16, IL-17, or IL-18 with MS risk.
Conclusions:
- Circulating IL-2Rα is causally associated with an increased risk of Multiple Sclerosis.
- These findings highlight IL-2Rα as a potential therapeutic target for MS.
- Further research is warranted to explore the mechanisms underlying IL-2Rα's role in MS.
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