Autoantibodies in the Postural Tachycardia Syndrome (P1.272)
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Abstract
OBJECTIVE: To ascertain the frequency of clinically-validated autoantibodies in sera of patients with Postural Tachycardia Syndrome (POTS), by systematically assessing organ-specific autoantibody profiles. BACKGROUND: We have occasionally noted IgG neuronal autoantibodies specific for ganglionic acetylcholine receptors, voltage-gated potassium channels (Kv1-type), calcium channels, and peripherin filament in clinically evaluating patients with POTS. It has recently been suggested that autoantibodies targeting vascular and cardiac adrenergic receptors are a major cause of POTS. METHODS: From a well-characterized group of patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011 we identified patients fulfilling clinical and autonomic criteria for POTS, and whose stored serum was available for comprehensive autoantibody testing: neural cation channels, thyroglobulin, thyroperoxidase and GAD65 (radio-immunoprecipitation assays), neural-specific plasma membrane, cytoplasmic and nuclear antibodies (standardized tissue-based indirect immunofluorescence assay on mouse cerebellum, midbrain, gut, and kidney) and muscle sarcomeric antibodies (ELISA). RESULTS: 33 patients fulfilled inclusion criteria. Median age was 27 years (range, 16-52); 27 were female (82[percnt]). IgG autoantibodies of at least one specificity were detected in 11 patients (33[percnt]); 5 patients (15[percnt]) had more than one autoantibody. Most common were thyroid antibodies, one or both (11 patients); one patient additionally had gastric parietal cell antibodies. CONCLUSIONS: Organ-specific autoantibodies are more common in patients with POTS (33[percnt]) than in a laboratory cohort of 161 healthy adult control subjects (4.4[percnt]) despite an older average age of the latter. Most of the detected autoantibodies were thyroid-specific. These findings and the female predominance in POTS support an autoimmune basis in about one third of cases. The neuronal autoantibodies encountered most frequently in autoimmune autonomic ganglionopathy appear to be rare in POTS. A focused investigation is now required to ascertain frequency and nature of neural-specific autoantibodies with pathogenetic potential in this syndrome. Supported by NIH (K23NS075141, P01NS44233, U54NS065736, UL1RR24150), Mayo Funds.
Disclosure: Dr. Singer has received license fee payments from Jacobus Pharmaceutical. Dr. Klein has nothing to disclose. Dr. Low has received personal compensation for activities with Chelsea Therapeutics, Pfizer Inc., and WR Medical Electronics Company as a consultant. Dr. Lennon stands to receive royalty payments for commercial assays to detect of Aquaporin 4-specific Autoantibody.
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