1. A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome
- Author
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Thariq Badiudeen, Elizabeth A. Forsythe, Graham Bennett, Hongliang Li, Xichun Yu, Marci Beel, Zachary Nuss, Kenneth E. Blick, Luis E. Okamoto, Amy C. Arnold, Sachin Y. Paranjape, Bonnie K. Black, Connor Maxey, David C. Kem, and Satish R. Raj
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). Methods: A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and β1AR-AAb in serum. Results: MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 ± 0.7 vs. 5.5 ± 0.9; P = 0.044) and in controls (4.1 ± 0.5 vs. 3.9 ± 0.6; P = 0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 ± 1.2 vs. 5.3 ± 1.0; P
- Published
- 2019
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