The possible involvement of sema3A and sema4A in the pathogenesis of multiple sclerosis
N Eiza1, M Garty2, E Staun-Ram3
1The Proteomic Unit, Bnai-Zion Medical Center, Haifa, Israel; The Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel.
Background:
Immune semaphorins are widely accepted to have functional impact on autoimmune diseases.
Objectives:
To assess the status of sema3A and sema4A in the pathogenesis of Multiple Sclerosis (MS).
Results:
Sema3A expression on (T regulatory cells)Tregs was decreased in MS patients, compared to healthy controls (35.85 ± 16.7% vs 88.27 ± 3.8%; p ≤ 0.001). Serum levels of sema3A were decreased in MS patients 2.95 ± 0.43 vs 18.67 ± 5.7 ng/ml in healthy individuals; p ≤ 0.001. Sema4A serum levels were increased in MS patients compared to healthy individuals (12.99 ± 8.6 vs 5.83 ± 3.91 ng/ml; p ≤ 0.001). Sema3A and sema4A serum levels were found to be in negative/positive correlation with MS disease severity (rs = 0.62, rs = -0.49, respectively).
Conclusion:
We show that sema3A is a regulatory molecule in MS, whereas sema4A is a stimulatory one. Targeting sema3A and sema4A could become a potential therapeutic approach in MS.
Insights
This study reveals that semaphorin 3A (sema3A) acts as a regulatory molecule in Multiple Sclerosis (MS), while semaphorin 4A (sema4A) is stimulatory. Targeting these molecules may offer new therapeutic avenues for MS patients.
Area of Science:
- Immunology
- Neuroscience
- Molecular Biology
Background:
- Immune semaphorins are implicated in autoimmune disease pathogenesis.
- Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
Purpose of the Study:
- To investigate the roles of semaphorin 3A (sema3A) and semaphorin 4A (sema4A) in the development of Multiple Sclerosis (MS).
Main Methods:
- Quantified sema3A expression on regulatory T cells (Tregs) in MS patients and healthy controls.
- Measured serum levels of sema3A and sema4A in MS patients and healthy individuals.
- Correlated sema3A and sema4A serum levels with MS disease severity.
Main Results:
- Decreased sema3A expression on Tregs and reduced serum sema3A levels were observed in MS patients compared to controls.
- Elevated serum sema4A levels were found in MS patients versus healthy individuals.
- Sema3A and sema4A serum levels showed significant negative and positive correlations with MS disease severity, respectively.
Conclusions:
- Sema3A functions as a regulatory molecule in MS, whereas sema4A acts as a stimulatory molecule.
- Targeting sema3A and sema4A presents a potential therapeutic strategy for managing MS.


