Autoimmune autonomic neuropathy

Abstract

Autoimmune diseases are among the most common causes of autonomic dysfunction. Autoimmune autonomic ganglionopathy (AAG) is a type of immune-mediated autonomic neuropathy. Around 50% of AAG cases are characterized by high levels of autoantibodies against ganglionic acetylcholine receptor (gAChR). As gAChR is known to mediate synaptic transmission in all autonomic ganglia, anti-gAChR antibodies inhibit this synaptic transmission, resulting in widespread autonomic dysfunction. Flow cytometric analysis of anti-gAChR antibody-mediated immunomodulation and live cell-based assays targeting the extracellular epitopes of the receptor have been reported as new approaches to measure the levels of this antibody and are expected to improve the specificity of antibody detection. The clinical presentation of anti-gAChR antibody-negative AAG cases is similar to that of anti-gAChR antibody-positive cases; however, the underlying mechanisms are still not fully understood. In anti-gAChR antibody-negative cases, intravenous methylprednisolone therapy is more effective than intravenous immunoglobulin therapy or plasma exchange, suggesting the involvement of cell-mediated immunity. Epidemiological studies, including the analysis of treatment efficacy in large numbers of patients, are needed. In this article we provide a review of our current understanding of anti-gAChR antibody-positive and -negative AAG and recent developments in the detection of anti-gAChR antibodies. In addition, acute autonomic and sensory neuropathy, which should be differentiated from AAG, is also outlined.