Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy.

Area of Science:

• Neurology
• Immunology
• Autonomic Neuroscience

Background:

• Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure.
• Ganglionic acetylcholine receptor antibody (gAChR-Ab) positivity indicates an autoimmune basis for AAG.
• Understanding the full clinical phenotype and response to immunotherapy is crucial for patient management.

Purpose of the Study:

• To characterize the clinical phenotype of gAChR-Ab positive AAG patients.
• To explore biomarkers for quantifying immunotherapy response in AAG.
• To evaluate the efficacy of multimodal testing in assessing autonomic dysfunction.

Main Methods:

• A cohort study of 13 gAChR-Ab positive patients with autonomic failure.
• Longitudinal assessment using cardiovascular, pupillary, urinary, sudomotor, lacrimal, and salivary testing.
• Composite Autonomic Symptom Score (COMPASS-31) questionnaires and orthostatic intolerance ratio calculation.

Main Results:

• All patients exhibited cardiovascular and pupillary impairments; many had sudomotor, urinary, and salivary dysfunction.
• Significant improvements were observed post-immunotherapy in orthostatic intolerance, heart rate response, pupillary function, saliva production, and COMPASS-31 scores.
• Skin sample analysis revealed nerve fiber loss and regeneration following immunotherapy.

Conclusions:

• gAChR-Ab positive AAG patients present with widespread sympathetic and parasympathetic autonomic failure.
• Immunotherapy leads to significant clinical and objective functional improvements.
• Quantitative autonomic biomarkers are essential for diagnosis, treatment guidance, and response monitoring in AAG.