Antibody signatures in patients with histopathologically defined multiple sclerosis patterns

Area of Science:

• Neuroimmunology
• Demyelinating Diseases
• Immunopathology

Background:

• Multiple sclerosis (MS) lesions exhibit diverse immunopathological patterns (I-III), indicating potential differences in disease mechanisms and treatment responses.
• Antibody profiles may correlate with these distinct MS lesion patterns, offering insights into pathogenesis.
• Baló's concentric sclerosis is a rare variant of MS characterized by concentric demyelination, with its specific immunopathology still under investigation.

Purpose of the Study:

• To investigate whether serum antibody reactivities can differentiate between the three main histological patterns of early active multiple sclerosis (MS) lesions.
• To explore potential associations between specific autoantigens and viral antigens with distinct MS immunopathological patterns, including Baló's concentric sclerosis.

Main Methods:

• A custom peptide microarray (over 700 peptides) was used to analyze serum antibody reactivities in 66 MS patients (classified into patterns I, II, and III, including Baló's), healthy controls, and patients with Sjögren's syndrome or stroke.
• Cell-based assays were employed for the detection of antibodies against aquaporin 1 (AQP1) and AQP4.
• Statistical analyses were performed to compare antibody reactivities between different patient groups and MS lesion patterns.

Main Results:

• No single peptide showed differential binding across all study cohorts; however, grouped peptide analysis revealed significant differences.
• Patients with pattern II MS lesions exhibited significantly higher reactivity to Nogo-A peptides compared to patterns I and III.
• Pattern III MS patients, including those with Baló's concentric sclerosis, showed significantly higher reactivities to AQP1 peptides and varicella zoster virus (VZV) peptides compared to other groups. Baló's patients specifically displayed distinct antibody signatures and loss of AQP1/AQP4 in lesions, despite no detected antibodies against conformational AQP1/AQP4.

Conclusions:

• Elevated Nogo-A peptide reactivity in pattern II MS may relate to axonal repair and remyelination processes.
• Increased AQP1 peptide reactivity in pattern III and Baló's MS suggests potential astrocytic damage and involvement of latent viral infections like VZV in peripheral immune activation.
• Antibody profiling holds promise for distinguishing MS subtypes and understanding their underlying immunopathological mechanisms.