Aging-dependent change in Th17 and cytokine response in multiple sclerosis

Area of Science:

• Neuroimmunology
• Autoimmune Diseases
• Aging Research

Background:

• Multiple sclerosis (MS) is a chronic central nervous system autoimmune disease.
• Inflammatory disease activity (DA) in people with MS (pwMS) diminishes with age.
• This decline prompts investigation into disease-modifying therapy (DMT) discontinuation in older pwMS due to risk-benefit considerations.

Purpose of the Study:

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

Main Methods:

• Clinical data from 669 pwMS (2017-2022) were analyzed.
• Peripheral blood mononuclear cells (PBMCs) from 80 pwMS were stimulated with MBP ex vivo.
• Interleukin-17 (IL-17) and Interferon-gamma (IFN-γ) levels were measured; associations with age and Annualized Relapse Rate (ARR) were analyzed using regression and mediation analyses.

Main Results:

• ARR declined with age in the cohort (p<0.001).
• MBP-stimulated IL-17 production decreased with age in women (p=0.04) but not men (p=0.73).
• MBP-driven IL-17 response partially mediated the association between older age and lower ARR (15.3-24.6% in men and women, respectively).
• Exploratory analyses revealed age-related differences in other cytokine concentrations, with some mediating the effect of age on ARR.

Conclusions:

• Diminished peripheral IL-17 response is a potential biological mechanism for aging-dependent decline in MS inflammatory DA.
• Further research is warranted to investigate this mechanism in pwMS.