Prognostic Biomarker Signature of Relapse in Neuromyelitis Optica Spectrum Disorders in the CIRCLES Observational...

Area of Science:

• Neuroimmunology
• Proteomics
• Biomarker Discovery

Background:

• Neuromyelitis optica spectrum disorders (NMOSD) are rare autoimmune CNS diseases characterized by relapses that cause progressive disability.
• Predicting and preventing NMOSD relapses is crucial for improving patient outcomes and quality of life.

Purpose of the Study:

• To identify individual and composite serum biomarkers that can predict NMOSD relapses.
• To establish a proteomic signature for stratifying relapse risk in NMOSD patients.

Main Methods:

• Longitudinal serum samples from NMOSD patients in the CIRCLES cohort were analyzed using high-resolution mass spectrometry.
• Statistical models, including logistic regression and Cox proportional hazards models, were employed to identify proteins associated with future relapses, controlling for clinical factors.

Main Results:

• A 10-protein signature (including Factor XI, Surfactant Protein B, C1RL, Filamin A, CETP, Cathelicidin, C4A, TFRC, IGKC, SAA2) was identified with consistent association across multiple models.
• This signature effectively stratified patients into high and low risk groups for subsequent NMOSD relapses.
• The abundance trajectories of these proteins varied before relapse, suggesting early predictive potential.

Conclusions:

• The identified 10-protein signature serves as a foundation for developing novel biomarkers to predict NMOSD relapses.
• Early prediction of NMOSD relapses can enable timely preventive therapeutic interventions.