Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

Area of Science:

• Biochemistry
• Immunology
• Neuroscience

Background:

• Multiple sclerosis (MS) is an inflammatory autoimmune central nervous system (CNS) disorder with unknown causes.
• N-glycosylation, the enzymatic addition of sugars to proteins, is implicated in MS pathogenesis.

Purpose of the Study:

• To investigate variations in N-glycosylation of plasma proteins and IgG in MS patients.
• To determine if N-glycan profiles can differentiate MS cases from healthy controls.

Main Methods:

• Chromatographic profiling and quantification of N-glycans from plasma and IgG.
• Analysis of 83 MS cases and 88 age- and sex-matched controls.
• Receiver Operating Characteristic (ROC) curve analysis for classification performance.

Main Results:

• Core fucosylation and high-mannose structures were significantly altered in IgG N-glycans of MS patients.
• Plasma protein N-glycome showed significant changes in fucosylated, sialylated, and galactosylated structures.
• N-glycan profiles achieved high classification accuracy (AUC 0.852 for plasma, 0.798 for IgG).

Conclusions:

• Multiple aspects of protein glycosylation are altered in MS, potentially increasing proinflammatory effects.
• N-glycan alterations demonstrate significant potential for classifying MS disease status.
• Further research is needed to clarify the role of N-glycans in MS development and their biomarker utility.