Relevant antibody subsets against MOG recognize conformational epitopes exclusively exposed in solid-phase ELISA

Area of Science:

• Neuroimmunology
• Autoimmunity
• Molecular Immunology

Background:

• Establishing a pathogenic role for circulating antibodies against myelin is challenging in multiple sclerosis (MS).
• Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies are implicated in demyelinating diseases, but their detection and pathogenic relevance remain debated.
• The conformation of MOG antigens significantly influences antibody recognition.

Purpose of the Study:

• To investigate the heterogeneity of anti-MOG antibodies in humans and non-human primates.
• To determine the optimal method for detecting pathogenic anti-MOG antibodies based on MOG antigen presentation.
• To understand why certain anti-MOG antibodies are difficult to detect using standard assays.

Main Methods:

• Comparison of ELISA (solid-phase) and liquid-phase assays using MOG protein in different conformations.
• Testing sera from 50 human subjects and plasma from Callithrix jacchus marmosets.
• Utilizing conformation-dependent monoclonal anti-MOG antibodies (mAbs).

Main Results:

• No human serum reactivity was observed against soluble MOG conformers, indicating dominant epitopes are not exposed in this form.
• Conformation-dependent mAbs showed no binding to soluble MOG, confirming epitope presentation issues.
• Pathogenic circulating anti-MOG antibodies in MP4-immune marmosets with demyelinating pathology were only detectable by ELISA.

Conclusions:

• Accurate detection of pathogenic anti-MOG antibodies necessitates methods that present MOG in a conformation similar to its natural state in myelin.
• Solid-phase assays, like ELISA, are superior for detecting conformation-dependent anti-MOG antibodies relevant to demyelinating diseases.
• Heterogeneity in anti-MOG antibody recognition underscores the importance of antigen presentation in immunological assays.