Multiple Sclerosis Progression: The Role of Genetic, Immune-Inflammatory, and Oxidative Stress Biomarkers
Multiple Sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by immune-mediated damage to the brain, spinal cord, and optic nerve. This study, conducted by Ana Paula Kallaur et al., evaluates the TNFβ NcoI polymorphism (rs909253) and immune-inflammatory, oxidative, and nitrosative stress (IO&NS) biomarkers as predictors of disease progression in MS.
The study included 212 MS patients and 249 healthy controls. The MS patients had a mean age of 42.7 years, with the control group having a mean age of 36.8 years. The study aimed to investigate the role of various biomarkers in predicting the progression of MS and the severity of disability.
Key Findings
TNFβ NcoI Polymorphism and Disease Progression: The TNFB1/B2 genotype was associated with a decreased risk of progression of pyramidal symptoms, suggesting a genetic influence on disease progression.
Cytokine Levels: Higher levels of TNF-α and IFN-γ were significantly associated with increased disability scores, indicating their role in disease progression. Conversely, IL-4 levels were lower in patients with more severe disease progression, highlighting its potential protective role.
Oxidative Stress Biomarkers: Elevated levels of oxidative stress markers such as carbonyl proteins and nitric oxide metabolites (NOx) were linked to increased disability. This supports the hypothesis that oxidative stress contributes to the pathogenesis of MS.
Disease-Modifying Drugs (DMDs): Treatments with IFN-β and glatiramer acetate reduced TNF-α levels but did not significantly affect other IO&NS biomarkers or the progression of the disease, suggesting that new treatments should also target oxidative stress.
Cytokines and MS Progression
TNF-α: This pro-inflammatory cytokine was found to be higher in patients with greater disability. TNF-α is known to be neurotoxic and plays a crucial role in the inflammatory process in MS.
IFN-γ: Another pro-inflammatory cytokine, IFN-γ, was also elevated in patients with higher disability scores. It contributes to neurotoxicity and is involved in the activation of various immune cells in MS.
IL-4: This cytokine, typically involved in anti-inflammatory responses, was lower in patients with severe disease, suggesting its protective role in MS.
IL-10: Elevated IL-10 levels were paradoxically associated with greater disability, possibly reflecting a compensatory anti-inflammatory response.
Oxidative Stress and Neurodegeneration
The study highlighted the significant role of oxidative stress in MS. Biomarkers such as carbonyl proteins and NOx were higher in patients with greater disability, indicating ongoing oxidative damage. This supports the idea that oxidative stress contributes to the degeneration of myelin and neuronal structures in MS.
Conclusion
This study underscores the importance of genetic, immune-inflammatory, and oxidative stress biomarkers in predicting the progression of MS. The findings suggest that targeting these cascades could be crucial in developing more effective treatments for MS. The association of the TNFB1/B2 genotype with reduced risk of pyramidal symptom progression also opens new avenues for genetic research in MS.
References:
Kallaur, A. P., Reiche, E. M. V., Oliveira, S. R., Simão, A. N. C., Pereira, W. L. D. C. J., Alfieri, D. F., ... & Maes, M. (2017). Genetic, immune-inflammatory, and oxidative stress biomarkers as predictors for disability and disease progression in multiple sclerosis. Molecular Neurobiology, 54, 31-44.
