Antibodies in neurological diseases: Established, emerging, explorative

Area of Science:

• Neuroimmunology
• Neurology
• Autoimmunity

Background:

• Autoantibodies targeting the nervous system have led to new disease classifications.
• Established autoantibodies have proven pathogenicity, guiding diagnostics and immunotherapy.
• The role of many other anti-neuronal autoantibodies in disease remains unclear but may modulate brain function.

Purpose of the Study:

• To propose a three-level classification for neurological autoantibodies: established, emerging, and explorative.
• To highlight the potential role of autoantibodies in conditions beyond typical autoimmune neurological diseases.
• To introduce the concept of the 'brain antibody-ome' and its implications for brain health.

Main Methods:

• Review of recent data on anti-neuronal autoantibodies and their pathogenicity.
• Analysis of clinical associations and experimental evidence.
• Proposal of a novel classification system for neurological autoantibodies.

Main Results:

• A three-level classification (established, emerging, explorative) based on pathogenicity and clinical association is proposed.
• This classification may help identify autoantibody involvement in autoimmune psychosis, dementia, cognitive impairment, and neurodegenerative diseases.
• Humoral autoimmunity, or the 'brain antibody-ome', may significantly influence neuronal function in both disease and healthy aging.

Conclusions:

• The proposed classification system can refine the understanding and diagnosis of neurological autoimmune disorders.
• The 'brain antibody-ome' concept suggests a broader role for autoantibodies in brain health and disease.
• Further research is needed to elucidate autoantibody pathogenicity at multiple levels for biomarker discovery and targeted therapies.