Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG...

Area of Science:

• Neuroimmunology
• Pediatric Neurology
• Autoimmune Diseases

Background:

• Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) accounts for 25% of pediatric acquired demyelinating syndrome (ADS).
• MOGAD can relapse in 40% of cases, mimicking multiple sclerosis (MS), a chronic neurodegenerative ADS.
• MOGAD is characterized by antibodies against MOG, while MS is MOG-antibody negative.

Purpose of the Study:

• To investigate immunological response differences in myelin oligodendrocyte glycoprotein (MOG) antigenic responses.
• To compare MOGAD, multiple sclerosis (MS), and control patients.
• To differentiate between relapsing and non-relapsing MOGAD subgroups.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from MOGAD, MS, and control patients were stimulated with recombinant human (rh)-MOG protein.
• T cell immunophenotypes, including CD4+ T cells, T helper (Th) cells (Th1, Th2, Th17), and regulatory T cells (Tregs), were analyzed via flow cytometry.
• Specific Treg subpopulations (naive, effector, non-suppressive) were quantified based on CD45RA and Foxp3 expression.

Main Results:

• MOGAD patients exhibited increased proportions of Th2 and Th17 cells upon rh-MOG stimulation compared to unstimulated cells.
• Th17 cell increase was significant in non-relapsing MOGAD (MOGNR) but not in relapsing MOGAD (MOGR).
• CD4+ Tregs increased in MOGNR but decreased in MOGR, with a significant decrease in CD45RA-Foxp3+ Tregs observed in MOGR.

Conclusions:

• CD4+ Th2 and Th17 cells play a role in the pathophysiology of pediatric MOGAD.
• Opposite Treg responses in relapsing versus non-relapsing MOGAD suggest a loss of MOG autoantigen tolerance in relapsing cases.
• This loss of tolerance may underlie the recurrent nature of MOGAD in pediatric patients.