Aging-dependent Change in Th17 and Cytokine Response in Multiple Sclerosis

Area of Science:

• Immunology
• Neuroscience
• Gerontology

Background:

• Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
• Inflammatory disease activity in people with MS (pwMS) tends to diminish with age.
• This age-related decline prompts investigation into the benefits versus risks of discontinuing disease-modifying therapies (DMTs) in older pwMS.

Purpose of the Study:

• To investigate if peripheral Myelin Basic Protein (MBP)-driven cytokine responses mediate the age-associated decline in MS inflammatory disease activity.
• To explore the relationship between age, MBP-stimulated cytokine production, and relapse rates in pwMS.

Main Methods:

• Analysis of clinical data from 669 pwMS (2017-2022).
• Isolation and ex vivo culture of peripheral blood mononuclear cells (PBMCs) from 80 pwMS with MBP stimulation.
• Assay of cytokine (IL-17, IFN-γ) production and analysis of associations between age, cytokine response, and annualized relapse rate (ARR) using regression and mediation analyses.

Main Results:

• Annualized relapse rate (ARR) declined with age in pwMS.
• MBP-stimulated IL-17 production decreased with age in women but not men.
• MBP-driven IL-17 response partially mediated the association between older age and lower ARR, particularly in women.

Conclusions:

• Diminished peripheral IL-17 response may be a biological mechanism for the age-dependent decline in MS inflammatory activity.
• These findings suggest a potential role for immune responses in modulating MS progression over time.
• Further research is warranted to elucidate the role of IL-17 in aging-related MS DA.