Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics

Area of Science:

• Neuroimmunology
• Autoimmune Neurology
• Central Nervous System (CNS) Disorders

Background:

• Neuronal septin autoimmunity is a potential cause of neurological dysfunction.
• The clinical significance and pathogenic mechanisms of septin-specific antibodies (septin-IgGs) require elucidation.

Purpose of the Study:

• To determine the clinical significance of neuronal septin autoimmunity.
• To evaluate the potential pathogenic effects of septin-IgGs on neuronal function.

Main Methods:

• Septin-IgGs were detected using indirect immunofluorescence assays and Western blot.
• Live rat hippocampal neuron assays assessed IgG binding and internalization.
• Murine cortical neuron function was analyzed via extracellular field potential recordings.

Main Results:

• Septin-IgGs were identified in 23 patients, correlating with specific neurological syndromes like cerebellar ataxia and encephalopathy.
• Patient IgGs bound to plasma membranes of live neurons and altered neuronal electrophysiologic activity.
• Eight of ten patients showed improvement after immunotherapy, indicating treatment responsiveness.

Conclusions:

• Septin-IgGs are predictive biomarkers for distinct, immunotherapy-responsive autoimmune CNS disorders.
• The observed live neuron binding and electrophysiologic effects support septin-specific pathophysiology in these conditions.