Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study

Weiming Sun; Jiawei Gui; Keqi Wan; Yize Cai; Xiangli Dong; Guohua Yu; Chafeng Zheng; Zhen Feng; Lang Shuai

doi:10.3389/fimmu.2024.1353034

Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study

Front Immunol. 2024 Mar 18:15:1353034. doi: 10.3389/fimmu.2024.1353034. eCollection 2024.

Authors

Weiming Sun^#^{1

2

3}, Jiawei Gui^#⁴, Keqi Wan^#^{1

2}, Yize Cai⁵, Xiangli Dong⁶, Guohua Yu^{1

2}, Chafeng Zheng^{1

2}, Zhen Feng^{1

2

3}, Lang Shuai^{1

2}

Affiliations

¹ Department of Rehabilitation Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
² The First Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, China.
³ Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
⁴ HuanKui Academy, Jiangxi Medical College, Nanchang University, Nanchang, China.
⁵ School of Public Policy, Nanchang University, Nanchang, China.
⁶ Department of Psychosomatic Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

^# Contributed equally.

Abstract

Objective: While observational studies link immune cells with post-stroke functional outcome, the underlying immune mechanisms are not well understood. Immune cell surface antigens are actively involved in the biological behavior of immune cells, investigating immune cell surface antigens could deepen our comprehension of their role and biological processes in stroke recovery. Therefore, we aimed to investigate the immunological basis of stroke outcome by exploring the causal relationship between immune cell surface antigens and functional outcome after ischemic stroke in a Mendelian randomization study.

Methods: Genetic variants related to immune cell surface antigens and post-stroke functional outcome were selected for two-sample Mendelian randomization (MR) analysis. 389 fluorescence intensities (MFIs) with surface antigens were included. Inverse variance weighted (IVW) modeling was used as the primary MR method to estimate the causal effect of exposure on the outcome, followed by several alternative methods and sensitivity analyses. Additional analysis of the association between immune cell surface antigens and risk of ischemic stroke for assessment of collider bias.

Results: We found that suggestive associations between CD20 on switched memory B cell (OR = 1.16, 95% CI: 1.01-1.34, p = 0.036) and PDL-1 on monocyte (OR = 1.32, 95% CI: 1.04-1.66, p = 0.022) and poor post-stroke functional outcome, whereas CD25 on CD39+ resting Treg (OR = 0.77, 95% CI: 0.62-0.96, p = 0.017) was suggestively associated with good post-stroke functional outcome.

Conclusion: The elevated CD20 on switched memory B cell, PDL-1 on monocyte, and CD25 on CD39+ resting Treg may be novel biomarkers and potential causal factors influencing post-stroke functional outcome.

Keywords: Mendelian randomization; immune cell; ischemic stroke; prognosis; surface antigens.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Surface
Causality
Humans
Ischemic Stroke* / genetics
Mendelian Randomization Analysis
Stroke* / genetics

Substances

Antigens, Surface

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was supported in part by grants from the Jiangxi Natural Science Foundation (20232BAB216090 and 20192BBG70016), Science and Technology Planning Project of Jiangxi Provincial Traditional Chinese Medicine Administration (2021B091 and 2020A0204) and Science and Technology Planning Project of Jiangxi Provincial Health Commission (202130164).