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外周免疫与多发性硬化症的风险和疾病严重程度之间的因果关联。

Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.

机构信息

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2024 Feb 8;15:1325938. doi: 10.3389/fimmu.2024.1325938. eCollection 2024.

DOI:10.3389/fimmu.2024.1325938
PMID:38390334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10881847/
Abstract

BACKGROUND

Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.

METHODS

Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.

RESULTS

MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4 T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25CD4 T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25CD4 T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25CD4 T cell in CD4 T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25CD8 T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4 T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).

CONCLUSIONS

This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.

摘要

背景

越来越多的证据表明免疫反应与多发性硬化症（MS）有关，但具体的免疫因素仍不清楚。

方法

采用孟德尔随机化（MR）方法探讨外周血血象特征、MS 风险及其严重程度之间的关联。然后，进一步对免疫细胞计数和循环细胞因子及生长因子进行亚组分析。

结果

MR 显示白细胞计数（OR [95%CI] = 1.26 [1.10,1.44]，P = 1.12E-03，P adjust = 3.35E-03）和淋巴细胞计数（OR [95%CI] = 1.31 [1.15,1.50]，P = 5.37E-05，P adjust = 3.22E-04）升高与 MS 风险增加相关。进一步分析表明，T 细胞绝对计数（OR [95%CI] = 2.04 [1.36,3.08]，P = 6.37E-04，P adjust = 2.19E-02）和 CD4 T 细胞绝对计数（OR [95%CI] = 2.11 [1.37,3.24]，P = 6.37E-04，P adjust = 2.19E-02）升高与 MS 风险增加相关。而增加 CD25CD4 T 细胞绝对计数（OR [95%CI] = 0.75 [0.66,0.86]，P = 2.12E-05，P adjust = 1.72E-03）、CD25CD4 T 细胞在 T 细胞中（OR [95%CI] = 0.79[0.70,0.89]，P = 8.54E-05，P adjust = 5.29E-03）、CD25CD4 T 细胞在 CD4 T 细胞中（OR [95%CI] = 0.80[0.72,0.89]，P = 1.85E-05，P adjust = 1.72E-03）和 CD25CD8 T 细胞在 T 细胞中（OR [95%CI] = 0.68[0.57,0.81]，P = 2.22E-05，P adjust = 1.72E-03）被证明对 MS 具有因果防御作用。对于疾病严重程度，一些与 CD4 T 细胞、Tregs 相关的特征与 MS 严重程度之间存在提示性关联。此外，IL-2Ra 水平升高对 MS 风险有不利影响（OR [95%CI] = 1.22 [1.12,1.32]，P = 3.20E-06，P adjust = 1.34E-04）。

结论

本研究表明外周血免疫细胞计数升高与 MS 之间存在遗传预测的因果关系。亚组分析显示外周免疫细胞具有特定的贡献，为进一步研究 MS 及其严重程度的潜在机制提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/9d36fbc83012/fimmu-15-1325938-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/da773314ed1d/fimmu-15-1325938-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/42a974f25ff3/fimmu-15-1325938-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/8641833c43d2/fimmu-15-1325938-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/9d36fbc83012/fimmu-15-1325938-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/da773314ed1d/fimmu-15-1325938-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/42a974f25ff3/fimmu-15-1325938-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/8641833c43d2/fimmu-15-1325938-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7d/10881847/9d36fbc83012/fimmu-15-1325938-g004.jpg

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