Details

Autor(en) / Beteiligte

• Badiudeen, Thariq
• Forsythe, Elizabeth A.
• Bennett, Graham
• Li, Hongliang
• Yu, Xichun
• Beel, Marci
• Nuss, Zachary
• Blick, Kenneth E.
• Okamoto, Luis E.
• Arnold, Amy C.
• Paranjape, Sachin Y.
• Black, Bonnie K.
• Maxey, Connor
• Kem, David C.
• Raj, Satish R.

Titel

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

Ist Teil von

• Journal of translational autoimmunity (Online), 2019-12, Vol.2, p.100006-100006, Article 100006

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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). 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. 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). 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. •Catecholamines can exist in stored frozen serum samples, even without antioxidants or preservatives.•MAO pre-treatment removes interference by endogenous catecholamines in serum.•POTS patients show elevated α1AR and β1AR activation by autoantibodies vs. Controls.