Optic neuritis anti-myelin basic protein synthetic peptide specificity.

Area of Science:

• Neuroimmunology
• Autoimmunity
• Demyelinating Diseases

Background:

• Elevated anti-myelin basic protein (anti-MBP) antibody titers are strongly associated with acute idiopathic unilateral optic neuritis and multiple sclerosis (MS) relapses.
• During acute optic neuritis, free/bound anti-MBP antibody ratios exceed unity, with high free antibody and low bound antibody levels.

Purpose of the Study:

• To investigate the characteristics and epitope specificity of anti-MBP antibodies in optic neuritis.
• To elucidate the potential role of anti-MBP antibodies in the mechanism of optic nerve demyelination.

Main Methods:

• Analysis of free/bound anti-MBP antibody ratios in cerebrospinal fluid during acute and recovery phases of optic neuritis.
• Neutralization assays using synthetic peptides of human MBP to determine anti-MBP epitope specificity.

Main Results:

• Free/bound anti-MBP ratios were above unity during acute optic neuritis and below unity during recovery.
• Anti-MBP antibodies from optic neuritis patients were neutralized by MBP synthetic peptides corresponding to amino acid residues 61-106.
• No reactivity was observed with peptides from residues 1-60 and 107-170, suggesting epitope localization within the 61-106 region.

Conclusions:

• Anti-MBP antibodies exhibit distinct free/bound ratios correlating with disease activity in optic neuritis.
• The primary epitope recognized by anti-MBP antibodies in optic neuritis is located within the 61-106 amino acid region of MBP.
• In situ binding of anti-MBP to this region may contribute to optic nerve demyelination in optic neuritis and MS.