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Genetically predicted association between immune cells and optic neuritis: evidence from a Mendelian randomization
Xiang Cao1,2,3, Zijiao Xu1,2,3, Zhencheng Ge1,2,3,4
1Department of Ophthalmology, Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
Current Eye Research
|July 18, 2026
Summary
This study found that specific immune cells, particularly HLA-DR++ monocytes, are causally linked to optic neuritis (ON) risk. These findings highlight potential biomarkers and therapeutic targets for this optic nerve inflammatory disease.
Area of Science:
- Immunology
- Genetics
- Neuro-ophthalmology
Background:
- Optic neuritis (ON) is an inflammatory optic nerve condition often preceding neurological disorders.
- Understanding the immune system's role in ON is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the causal relationship between various immune cells and the risk of developing optic neuritis.
- To identify specific immune cell types that may serve as biomarkers or therapeutic targets for ON.
Main Methods:
- A bidirectional Mendelian randomization (MR) approach was employed using genetic data from Sardinian and FinnGen cohorts.
- Genetic variants associated with 731 immune cell types were analyzed against ON data.
- Inverse-variance weighted (IVW) analysis was the primary method, with sensitivity analyses for robustness.
Main Results:
- Eleven immune cell types showed a significant association with ON risk.
- The proportion of human leukocyte antigen receptor (HLA-DR)++ monocytes was identified as a strong positive risk factor for ON (OR = 1.828).
- Robustness was confirmed through heterogeneity, pleiotropy tests, and multivariate MR analysis, with HLA-DR++ monocytes remaining significant after corrections.
Conclusions:
- Specific immune cells, especially HLA-DR++ monocytes, play a critical role in the pathogenesis of optic neuritis.
- These findings offer genetic insights into immune-mediated ON mechanisms.
- Identified immune cells represent potential biomarkers and therapeutic targets for ON.