Ganglionic Acetylcholine Receptor Antibodies in Postural Tachycardia Syndrome

2021 ◽  
Vol 11 (4) ◽  
pp. e397-e401
Author(s):  
Meredith Bryarly ◽  
Satish R. Raj ◽  
Lauren Phillips ◽  
Linda S. Hynan ◽  
Luis E. Okamoto ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Clinical Information ◽  
Postural Tachycardia Syndrome ◽  
Healthy Controls ◽  
Serum Samples ◽  
Postural Tachycardia ◽  
Healthy Control ◽  
Low Levels ◽  
Antibody Levels ◽  
Receptor Antibodies

ObjectivePostural tachycardia syndrome (POTS), the most common form of dysautonomia, may be associated with autoimmunity in some cases. Autoantibodies against the ganglionic acetylcholine receptor (gAChR) have been reported in a minority of patients with POTS, but the prevalence and clinical relevance is unclear.MethodsClinical information and serum samples were systematically collected from participants with POTS and healthy control volunteers (n = 294). The level of positive gAChR antibodies was classified as very low (0.02–0.05 nmol/L), low (0.05–0.2 nmol/L), and high (>0.2 nmol/L).ResultsFifteen of 217 patients with POTS (7%) had gAChR antibodies (8 very low and 7 low). Six of the 77 healthy controls (8%) were positive (3 very low and 3 low). There were no clinical differences between seropositive and seronegative patients with POTS.ConclusionsPrevalence of gAChR antibody did not differ between POTS and healthy controls, and none had high antibody levels. Patients with POTS were not clinically different based on seropositivity. Low levels of gAChR antibodies are not clinically important in POTS.

Abstract P157: Assessment of Vascular Endothelial Function in Postural Tachycardia Syndrome and Healthy Controls

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jorge Celedonio ◽  
Victor Nwazue ◽  
Rocio Figueroa ◽  
Sachin Paranjape ◽  
Bonnie Black ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Autonomic Function ◽  
Renin Activity ◽  
Cerebral Hypoperfusion ◽  
Postural Tachycardia Syndrome ◽  
Flow Mediated Dilation ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Postural Tachycardia ◽  
Healthy Control

Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in HR and symptoms consistent with cerebral hypoperfusion while upright. Increased sympathetic activity may contribute to this condition and may also impair nitric oxide (NO)-function. We evaluated NO function using flow-mediated dilation (FMD) and Peripheral Artery Tonometry (PAT) in POTS patients and age-matched controls. We studied 16 POTS patients (30±2 years, BMI 22.3±1 kg/m 2 ) and 7 healthy control subjects (HC; 31±2 years, BMI 22.1±1 kg/m 2 ). Medications affecting BP, blood volume, the immune system, and autonomic function, were withheld for ≥5 half-lives. All subjects followed the same low-monoamine, caffeine-free diet for ≥3 days before testing. Endothelial function was measured as the percentage change in FMD (%FMD) and using the reactive hyperemic index (RHI) for PAT. We also measured autonomic function, plasma levels of catecholamines, renin activity (PRA) and aldosterone. We found that POTS patients had a significantly blunted FMD (6.11±0.8 vs. 9.67±1.6 %, P=0.049, figure), compared to healthy controls. This blunted FMD response was similar as what our group has reported in obese hypertensive females (N=13, 5.7±0.9%, figure). Also, as expected they had higher upright HR (121±6 vs. 90±6 bpm, for POTS and HC, P=0.020). There were no differences in PAT (2.08±0.12, vs. 1.8±0.13 RHI, for POTS and HC, P=0.168). There were no differences in norepinephrine (765±150 vs. 545±39 pg/mL, P=0.955), renin activity (5.3±1.3 vs. 5.2±1.6 ng/mL/hr, P=0.735) or aldosterone (19.6±3.8 vs. 15.9±5.5 ng/dL, P=0.129).

scholarly journals Serum adipokines as non-invasive biomarkers in Crohn’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lorena Ortega Moreno ◽  
Ancor Sanz-Garcia ◽  
Marina J. Fernández de la Fuente ◽  
Ricardo Arroyo Solera ◽  
Samuel Fernández-Tomé ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
High Concentration ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Non Invasive ◽  
Healthy Control

Abstract Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.

scholarly journals Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
C1 Inhibitor ◽  
Serum Samples ◽  
Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

scholarly journals Immunity to diphtheria in Siena

1997 ◽  
Vol 119 (2) ◽  
pp. 203-208 ◽  
Author(s):  
R. GASPARINI ◽  
T. POZZI ◽  
E. FRAGAPANE ◽  
R. SEVERINI ◽  
C. CELLESI ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Total Population ◽  
Young Population ◽  
Protective Level ◽  
Serum Samples ◽  
Test Elisa ◽  
Diphtheria Antitoxin ◽  
Low Levels ◽  
Antibody Levels ◽  
Apparently Healthy

The aim of this study, carried out in 1993, was to evaluate diphtheria immunity in Siena. Diphtheria antitoxin levels were measured by means of the immunoenzymatic test (ELISA) in serum samples of 602 apparently healthy subjects (239 males and 363 females) of all ages residing in Siena. According to widely used criteria, 6% of the total population were susceptible to diphtheria (antibody levels <0·01 IU/ml), 71% had basic protection (0·01–0·09 IU/ml) and 23% were fully protected ([ges ]0·1 IU/ml). The results suggested that a high proportion of young population had a protective level of immunity against diphtheria, that susceptibility increased with age and a smaller proportion of males (2·9%) than females (8·3%) were unprotected; this difference was statistically significant. Our results suggest that it may be useful to revaccinate adults with low levels of diphtheria toxoid so that the percentage that remains unprotected does not put the community at risk of an outbreak of diphtheria.

The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome

2014 ◽  
Vol 36 (1) ◽  
pp. 165-170 ◽  
Author(s):  
Jiawei Li ◽  
Qingyou Zhang ◽  
Ying Liao ◽  
Chunyu Zhang ◽  
Hongjun Hao ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Postural Tachycardia Syndrome ◽  
Receptor Antibody ◽  
Postural Tachycardia ◽  
Acetylcholine Receptor Antibody

scholarly journals Baroreceptor unloading in postural tachycardia syndrome augments peripheral chemoreceptor sensitivity and decreases central chemoreceptor sensitivity

2011 ◽  
Vol 301 (1) ◽  
pp. H173-H179 ◽  
Author(s):  
Indu Taneja ◽  
Marvin S. Medow ◽  
Debbie A. Clarke ◽  
Anthony J. Ocon ◽  
Julian M. Stewart
Keyword(s):  
Minute Ventilation ◽  
Postural Tachycardia Syndrome ◽  
Healthy Controls ◽  
Peripheral Chemoreceptor ◽  
Postural Tachycardia ◽  
Chemoreflex Sensitivity ◽  
The Difference ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
Upright Tilt

While orthostatic tachycardia is the hallmark of postural tachycardia syndrome (POTS), orthostasis also initiates increased minute ventilation (V̇e) and decreased end-tidal CO2 in many patients. We hypothesized that chemoreflex sensitivity would be increased in patients with POTS. We therefore measured chemoreceptor sensitivity in 20 POTS (16 women and 4 men) and 14 healthy controls (10 women and 4 men), 16–35 yr old by exposing them to eucapneic hyperoxia (30% O2), eucapneic hypoxia (10% O2), and hypercapnic hyperoxia (30% O2 + 5% CO2) while supine and during 70° head-upright tilt. Heart rate, mean arterial pressure, O2 saturation, end-tidal CO2, and V̇e were measured. Peripheral chemoreflex sensitivity was calculated as the difference in V̇e during hypoxia compared with room air divided by the change in O2 saturation. Central chemoreflex sensitivity was determined by the difference in V̇e during hypercapnia divided by the change in CO2. POTS subjects had an increased peripheral chemoreflex sensitivity (in l·min−1·%oxygen−1) in response to hypoxia (0.42 ± 0.38 vs. 0.19 ± 0.17) but a decreased central chemoreflex sensitivity (l·min−1·Torr−1) CO2 response (0.49 ± 0.38 vs. 1.04 ± 0.18) compared with controls. CO2 sensitivity was also reduced in POTS subjects when supine. POTS patients are markedly sensitized to hypoxia when upright but desensitized to CO2 while upright or supine. The interactions between orthostatic baroreflex unloading and altered chemoreflex sensitivities may explain the hyperventilation in POTS patients.

scholarly journals A Flow Cytometric Assay to Detect Functional Ganglionic Acetylcholine Receptor Antibodies by Immunomodulation in Autoimmune Autonomic Ganglionopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicolás Urriola ◽  
Judith M. Spies ◽  
Katrina Blazek ◽  
Bethan Lang ◽  
Stephen Adelstein
Keyword(s):  
Acetylcholine Receptor ◽  
Lupus Erythematosus ◽  
False Positive ◽  
Flow Cytometric Analysis ◽  
Healthy Controls ◽  
Flow Cytometric Assay ◽  
Serum Samples ◽  
Autoimmune Autonomic Ganglionopathy ◽  
Receptor Modulation ◽  
Flow Cytometric

Autoimmune Autonomic Ganglionopathy (AAG) is an uncommon immune-mediated neurological disease that results in failure of autonomic function and is associated with autoantibodies directed against the ganglionic acetylcholine receptor (gnACHR). The antibodies are routinely detected by immunoprecipitation assays, such as radioimmunoassays (RIA), although these assays do not detect all patients with AAG and may yield false positive results. Autoantibodies against the gnACHR exert pathology by receptor modulation. Flow cytometric analysis is able to determine if this has occurred, in contrast to the assays in current use that rely on immunoprecipitation. Here, we describe the first high-throughput, non-radioactive flow cytometric assay to determine autoantibody mediated gnACHR immunomodulation. Previously identified gnACHR antibody seronegative and seropositive sera samples (RIA confirmed) were blinded and obtained from the Oxford Neuroimmunology group along with samples collected locally from patients with or without AAG. All samples were assessed for the ability to cause gnACHR immunomodulation utilizing the prototypical gnACHR expressing cell line, IMR-32. Decision limits were calculated from healthy controls, and Receiver Operating Characteristic (ROC) curves were constructed after unblinding all samples. One hundred and ninety serum samples were analyzed; all 182 expected negative samples (from healthy controls, autonomic disorders not thought to be AAG, other neurological disorders without autonomic dysfunction and patients with Systemic Lupus Erythematosus) were negative for immunomodulation (&lt;18%), as were the RIA negative AAG and unconfirmed AAG samples. All RIA positive samples displayed significant immunomodulation. There were no false positive or negative samples. There was perfect qualitative concordance as compared to RIA, with an Area Under ROC of 1. Detection of Immunomodulation by flow cytometry for the identification of gnACHR autoantibodies offers excellent concordance with the gnACHR antibody RIA, and overcomes many of the shortcomings of immunoprecipitation assays by directly measuring the pathological effects of these autoantibodies at the cellular level. Further work is needed to determine the correlation between the degree of immunomodulation and disease severity.

scholarly journals Diurnal variability in orthostatic tachycardia: implications for the postural tachycardia syndrome

2011 ◽  
Vol 122 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Jordan A. Brewster ◽  
Emily M. Garland ◽  
Italo Biaggioni ◽  
Bonnie K. Black ◽  
John F. Ling ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Supine Position ◽  
Healthy Subjects ◽  
Postural Tachycardia Syndrome ◽  
Healthy Controls ◽  
Diurnal Variability ◽  
Postural Tachycardia ◽  
Clinical Research Center

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.

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