A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome.

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 ​< ​0.001) and β1AR-AAb (5.7 ​± ​1.8 vs. 4.1 ​± ​0.9; P ​< ​0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P ​= ​0.007) and β1AR-AAb activity (52% vs. 2%; P ​< ​0.001).

CONCLUSIONS:

The co-presence of norepinephrine in serum samples can artifactually elevate α1AR and β1AR activity, which can be avoided by serum pre-treatment with MAO. Using this novel bioassay, we show that POTS patients have increased α1AR-AAb and β1AR-AAb activity compared to healthy controls in the largest POTS cohort reported to-date.

• Authors: 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, Satish R Raj
• Journal: Journal of translational autoimmunity (J Transl Autoimmun) Vol. 2 Pg. 100006 (Dec 2019) ISSN: 2589-9090 [Electronic] Netherlands
• PMID: 32743496 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors.