# Elucidating the Causal Relationships Between B Cells, Dendritic Cells, and Multiple Sclerosis Pathogenesis

## TL;DR

This study explores how specific immune cells, like B cells and dendritic cells, contribute to multiple sclerosis, identifying potential new treatment targets.

## Contribution

The study uses Mendelian randomization to establish causal relationships between immune cell traits and MS, revealing novel genetic and functional insights.

## Key findings

- Causal links between B cells and dendritic cells with MS susceptibility were identified.
- 61 pleiotropic genes associated with MS were discovered, including those involved in B-cell antigen presentation and HLA pathways.
- Alterations in immune cell populations after MS onset suggest potential biomarkers for early diagnosis.

## Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that leads to significant disability, with its precise etiology still not fully understood. Recent studies indicate the crucial role of immune cells in MS pathogenesis. However, traditional research often focuses on major immune cell populations, potentially neglecting the roles of newly identified immune cell subsets with distinct receptors and functions. Moreover, conventional observational studies are prone to biases, hindering the establishment of definitive causal relationships. This study aims to investigate the causal relationships between 731 immune cell traits and MS susceptibility using Mendelian randomization (MR) analysis to provide more robust insights into the underlying mechanisms of MS.

We performed MR analyses to assess associations between various immune cell traits and MS risk. Following this, we explored the molecular mechanisms of the significant associations, focusing particularly on B‐cell antigen presentation and the involvement of human leukocyte antigen (HLA) pathways.

Our analysis revealed specific causal links between B cells and dendritic cells with MS susceptibility. We identified 61 pleiotropic genes associated with MS. Notably, B‐cell antigen presentation and HLA‐related pathways play pivotal roles in MS pathogenesis. Additionally, alterations in immune cell populations post‐MS onset were observed, suggesting potential biomarkers for early diagnosis.

This study offers a comprehensive examination of immune cell contributions to MS pathogenesis, identifying potential therapeutic targets and diagnostic markers. Given the side effects of anti‐B cell monoclonal antibodies in MS treatment, our findings propose avenues for more precise therapeutic strategies aimed at minimizing adverse effects.

This study presents an integrative pipeline linking immune cell traits to multiple sclerosis (MS) susceptibility. Genome‐wide association and Mendelian randomization analyses revealed causal roles of immune cells in MS risk. Colocalization and pleiotropy mapping identified candidate genes, further refined through functional annotation, network analysis, and druggability assessment.