Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months

Area of Science:

• Immunology
• Neuroimmunology
• Cellular Immunology

Background:

• Alemtuzumab is an effective therapy for relapsing-remitting multiple sclerosis (RRMS).
• Understanding its immunomodulatory effects on T-cell subsets and cytokine profiles is crucial for long-term efficacy assessment.

Purpose of the Study:

• To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules.
• To assess these changes over a 24-month follow-up period after alemtuzumab treatment in RRMS patients.

Main Methods:

• Multicenter follow-up of 29 alemtuzumab-treated RRMS patients from the CARE-MS I and II trials.
• Analysis of peripheral blood samples at 0, 6, 12, 18, and 24 months.
• Evaluation of mRNA levels of 26 immunologic molecules, Th1, Th17, and Treg cell percentages, and myelin basic protein (MBP)-specific Treg suppressor activity.

Main Results:

• Persistent increase in anti-inflammatory cytokines (IL-10, IL-27, TGF-β) and decrease in pro-inflammatory molecules.
• Treg cell percentage and suppressive activity against MBP-specific Th1 and Th17 cells significantly increased by month 24.
• Peripheral blood CD4+ cell percentage remained lower than baseline, while Th1 and Th17 percentages did not significantly change.

Conclusions:

• Alemtuzumab's long-lasting benefit in RRMS may stem from a shift towards inflammation inhibition.
• Reconstitution of T-cell subsets, including expanded Treg cells with enhanced suppressive function, contributes to therapeutic effects.