A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome
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 pa...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Journal of Translational Autoimmunity |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589909019300061 |
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doaj-09ebaf1b5cb44593a243f29a23476a74 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome Journal of Translational Autoimmunity |
| author_facet |
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 |
| author_sort |
Thariq Badiudeen |
| title |
A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| title_short |
A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| title_full |
A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| title_fullStr |
A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| title_full_unstemmed |
A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| title_sort |
functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndrome |
| publisher |
Elsevier |
| series |
Journal of Translational Autoimmunity |
| issn |
2589-9090 |
| publishDate |
2019-12-01 |
| description |
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. Keywords: Postural tachycardia syndrome, Orthostatic tachycardia, Heart rate, Autoantibody, Adrenergic receptor |
| url |
http://www.sciencedirect.com/science/article/pii/S2589909019300061 |
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doaj-09ebaf1b5cb44593a243f29a23476a742020-11-25T02:29:59ZengElsevierJournal of Translational Autoimmunity2589-90902019-12-012A functional cell-based bioassay for assessing adrenergic autoantibody activity in postural tachycardia syndromeThariq Badiudeen0Elizabeth A. Forsythe1Graham Bennett2Hongliang Li3Xichun Yu4Marci Beel5Zachary Nuss6Kenneth E. Blick7Luis E. Okamoto8Amy C. Arnold9Sachin Y. Paranjape10Bonnie K. Black11Connor Maxey12David C. Kem13Satish R. Raj14Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, T2N 4N1, CanadaDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, T2N 4N1, CanadaDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USAAutonomic Dysfunction Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Neural & Behavioral Sciences, Penn State College of Medicine, Hershey, PA, 17033, USAAutonomic Dysfunction Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USAAutonomic Dysfunction Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USADepartment of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, T2N 4N1, CanadaDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USADepartment of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, T2N 4N1, Canada; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Corresponding author. University of Calgary, GAC70 HRIC Bldg, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.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. Keywords: Postural tachycardia syndrome, Orthostatic tachycardia, Heart rate, Autoantibody, Adrenergic receptorhttp://www.sciencedirect.com/science/article/pii/S2589909019300061 |