A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome.
J Transl Autoimmun
; 2: 100006, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-32743496
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 ß1AR-AAb in serum.RESULTS:
MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 â± â0.7 vs. 5.5 â± â0.9; P â= â0.044) and in controls (4.1 â± â0.5 vs. 3.9 â± â0.6; P â= â0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 â± â1.2 vs. 5.3 â± â1.0; P â< â0.001) and ß1AR-AAb (5.7 â± â1.8 vs. 4.1 â± â0.9; P â< â0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P â= â0.007) and ß1AR-AAb activity (52% vs. 2%; P â< â0.001).CONCLUSIONS:
The co-presence of norepinephrine in serum samples can artifactually elevate α1AR and ß1AR 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 ß1AR-AAb activity compared to healthy controls in the largest POTS cohort reported to-date.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
J Transl Autoimmun
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá