A Differential Proteomic Analysis on Patient Sera with Neuromyelitis Spectrum Disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Suggested Shared and Distinct Disease Mechanisms

Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are two types of autoimmune-mediated central nervous system (CNS) inflammatory demyelinating diseases that have similar clinical manifestations but with different pathogenesis and prognosis. Here, we reported on a differential proteomic analysis on the patient sera with the two diseases. Serum samples of 25 aquaporin-4 (AQP4)-IgG+ NMOSD patients, 16 MOGAD patients, and 8 healthy individuals were submitted to shotgun analysis using nano-LC-MS/MS. Totally, 584 nonredundant proteins were identified and quantified, among which 340 proteins were detected in at least three samples per group. Statistical analysis revealed 40 proteins had significant difference in at least one group-pair comparison (fold change >1.2 or <0.83 and multiple-sample test ANOVA-q < 0.05). Also, 38 proteins were detected only in the patient groups and not in the healthy controls. Bioinformatic analysis on these 78 proteins revealed that disturbance of the immune system, hemostasis processes, and carbohydrate metabolism occurred in both diseases, while the dysregulation patterns suggested different mechanisms. We expect this work would provide useful information to improve the understanding of the mechanisms of NMOSD and MOGAD and suggest potential diagnostic markers and treatment targets.