The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and...

Area of Science:

• Immunology
• Neuroimmunology
• Autoimmune Diseases

Background:

• Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune CNS disease.
• Pathogenic antibodies against aquaporin-4 (AQP4-Ab) drive NMOSD.
• Current treatments include immunosuppressants and B-cell depletion (rituximab).

Purpose of the Study:

• Characterize circulating T follicular helper (Tfh) cell subsets in NMOSD patients.
• Analyze the impact of NMOSD treatments on Tfh subsets.
• Investigate the role of Tfh subsets in NMOSD pathophysiology.

Main Methods:

• Flow cytometry analysis of Tfh subsets (Tfh1, Tfh2, Tfh17, Tfr) in 25 NMOSD patients.
• Comparison of Tfh subset distribution in untreated NMOSD patients, treated NMOSD patients, and healthy controls.
• Analysis of treatment effects (rituximab, azathioprine, mycophenolate mofetil) on Tfh polarization.

Main Results:

• Untreated NMOSD patients show Tfh polarization towards B-cell helper subsets (increased Tfh17, elevated (Tfh2+Tfh17)/Tfh1 ratio).
• NMOSD patients exhibit decreased T follicular regulatory (Tfr) cells and Tfh1 cells.
• Rituximab treatment normalized Tfh polarization towards healthy control levels; azathioprine and mycophenolate mofetil showed a similar trend.

Conclusions:

• NMOSD is associated with an imbalanced Tfh subset profile that promotes B-cell differentiation and sustained antibody production.
• Tfh and Tfr cells represent potential upstream therapeutic targets for NMOSD.
• Findings offer new insights into NMOSD pathophysiology and immune dysregulation.