Ganglionic Acetylcholine Receptor Antibodies in Postural Tachycardia Syndrome

Bryarly, Meredith; Raj, Satish R.; Phillips, Lauren; Hynan, Linda S.; Okamoto, Luis E.; Arnold, Amy C.; Paranjape, Sachin Y.; Vernino, Megan; Black, Bonnie K.; Vernino, Steven

doi:10.1212/cpj.0000000000001047

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…These three patients all had low levels of gAChR antibodies (<0.12 nmol/L). The lack of association between gAChR antibodies and POTS was also seen in a study of POTS patients in the community, which detected seropositivity in only 7% of patients, a figure comparable to that found in healthy controls [ 29 ]. Taken together, these findings suggest that gAChR antibodies are rarely elevated in POTS patients and are unlikely to be a relevant marker for distinguishing between subtypes of POTS.…”

Section: Discussionmentioning

confidence: 57%

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome

Zhang¹,

Mayuga²,

Shields³

et al. 2022

Cureus

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Purpose: No formal diagnostic criteria exist for the neuropathic subtype of postural orthostatic tachycardia syndrome (POTS). Skin biopsy and quantitative sudomotor axon reflex testing (QSORT) are preferred methods of assessment for autonomic small fiber neuropathy (SFN). This study characterizes the utility of these testing methods at a tertiary center and identifies clinical features associated with abnormal testing.Methods: Medical records of 2658 patients undergoing tilt table testing at a single institution between June 2018 and December 2020 were reviewed. Patients with postural orthostatic tachycardia syndrome were included for analysis of intraepidermal nerve fiber density (IENFD), sweat output, comorbidities, symptoms, measures of cardiovascular autonomic function, and serum antibody levels.Results: 356 patients (90% female, mean age 31 ± 10) met the diagnostic criteria for postural orthostatic tachycardia syndrome. Of 211 patients who underwent quantitative sudomotor axon reflex testing, 70 (33%) demonstrated reduced sweat output. These patients were more likely to demonstrate sympathetic impairment during the Valsalva maneuver. Of 80 patients who underwent skin biopsies, 19 (24%) demonstrated reduced intraepidermal nerve fiber density. These patients tended to be older and have reduced heart rate variability during deep breathing. Neither test was associated with specific serum antibodies, symptoms, or comorbidities, though there was a trend toward higher rates of comorbid autoimmune disease in patients with abnormal testing. Conclusion: A subset of patients with postural orthostatic tachycardia syndrome have evidence of small fiber neuropathy. These patients tend to have impaired cardiovascular autonomic function but are otherwise similar to patients with no evidence of small fiber neuropathy.

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Section: Discussionmentioning

confidence: 57%

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome

Zhang¹,

Mayuga²,

Shields³

et al. 2022

Cureus

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“…8 A number of studies have explored this area by studying the prevalence and activity of autoantibodies against cardiovascular G protein-coupled receptors (GPCRs) in patients with POTS. 7,[9][10][11][12][13][14][15] Some studies have found increased concentrations of GPCR autoantibodies, as well as a variety of others, in patients with POTS. 10,11 Despite this extensive research, there is no consensus as to what role autoantibodies against GPCRs and other receptors play in the pathophysiology of POTS.…”

mentioning

confidence: 99%

“…In addition, autoantibodies have been found in healthy controls as well as in patients. 15 Most studies of GPCR autoantibodies in POTS have had small samples sizes and have lacked appropriate internal controls. 16 Using a relatively large multicenter cohort, we sought to test the null hypothesis that GPCR autoantibody concentrations are not different between patients with POTS and healthy controls using an established, commercially available enzyme-linked immunosorbent assay (ELISA).…”

mentioning

confidence: 99%

Detection of G Protein–Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology

et al. 2022

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Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein–coupled receptors between patients with POTS and healthy controls. Methods: Sera were collected from 116 patients with POTS (91% female; medium age, 29 years) and 81 healthy controls (84% female; medium age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay. Results: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls. Conclusions: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay–derived autoantibody concentrations to cardiovascular G protein–coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.

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“…In clinical practice, 30-50% of patients with AAG have a high antibody titer. However, lower titer of α3-nAChR antibodies might be present in other autonomic syndromes including postural tachycardia syndrome [8], peripheral autonomic neuropathies, and more localized forms of autonomic impairment such as pure gastrointestinal motility failure. The clinical relevance of the α3-nAChR antibodies at low titer is unclear.…”

Section: Doctor What About These Antibody Results?mentioning

confidence: 99%

Implantable neurostimulators for neurogenic orthostatic hypotension: the wave of the future? and other updates on recent autonomic research

2022

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Ganglionic Acetylcholine Receptor Antibodies in Postural Tachycardia Syndrome

Cited by 12 publications

References 15 publications

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome

Detection of G Protein–Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology

Implantable neurostimulators for neurogenic orthostatic hypotension: the wave of the future? and other updates on recent autonomic research

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