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The Causal Relationship between Antibody Immune Response and Ischemic Stroke: A Mendelian Randomization Analysis
Chunshu Rong1, Zhen Wei1,2, Yuetong Zhao3
1Department of Encephalopathy, Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130021, China.
Introduction:
Recognizing the risk factors associated with Ischemic Stroke (IS) is essential for its prevention. Currently, there are no studies exploring the causal link between antibodymediated immune responses and IS. This Mendelian Randomization (MR) study further examines whether a causal relationship exists between antibody-mediated immune responses and IS, and offers evidence supporting causality.
Method:
Data on antibody-mediated immune responses came from 9,724 subjects (European ethnicity) as the research participants and who collected their serum samples for microbiological serological analysis. By employing a multiplex antigen detection technique, the total antibody concentrations against various antigens in the samples were systematically measured. IS data were acquired from the MEGASTROKE consortium, which provides stroke-related summary data based on genomewide association studies, encompassing 40,585 stroke patients and 406,111 control individuals (European ethnicity). MR analysis was conducted to estimate the associations between antibodymediated immune responses (exposure) and IS (outcome) risk.
Results:
The inverse variance weighted analysis revealed that 26 antibody-mediated immune responses were associated with IS in three subtypes in genetic prediction. There is an effect of anti- Chlamydia trachomatis, anti-cytomegalovirus, anti-human herpesvirus, varicella-zoster virus, anti- Merkel cell polyomavirus, Epstein-Barr virus, anti-Helicobacter pylori, anti-JC polyomavirus, and anti-Toxoplasma antibodies on the three subtypes of IS in genetic prediction.
Discussion:
In large-artery atherosclerosis and small-vessel stroke, a high antibody level may be accompanied by direct endothelial cell invasion and vascular inflammation. In cardioembolic stroke, however, high antibody levels may instead reflect efficient viral latency maintenance with reduced systemic inflammation or hypercoagulability associated with cardiogenic embolism. In addition, different antigenic components (momp A vs. total IgG) against C. pneumoniae showed opposite associations.
Conclusion:
The research provides new genetic evidence for the complex role of antibody-mediated immune responses in the etiology of stroke, suggesting that pathogen-specific immune responses may serve as differentiated risk markers and potential intervention targets for different subtypes of stroke.
