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Antiadrenergic autoimmunity in postural tachycardia syndrome
Open accessAbstract
AIMS: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). METHODS AND RESULTS: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity. CONCLUSION: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.
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TL;DR
IgG from patients with postural tachycardia syndrome (POTS) showed higher direct activation of α1-adrenergic and β1/2-adrenergic receptors than IgG from recurrent vasovagal syncope (VVS) patients or healthy controls, and also altered receptor responsiveness to phenylephrine and isoproterenol. These antiadrenergic autoantibody effects correlated with upright heart rate and support an autoimmune contribution to POTS pathophysiology.
Key findings
- Among 17 POTS patients, direct receptor activation was found in 8/17 for α1AR (47%), 11/17 for β1AR (65%), and 12/17 for β2AR (71%); none of these autoantibodies were found in VVS patients or healthy controls.
- Mean autoantibody activity was significantly higher in POTS than in VVS and controls for α1AR (0.31 ± 0.07 vs. 0.24 ± 0.04 and 0.23 ± 0.04; P=0.029 and 0.004), β1AR (1840 ± 186 vs. 1578 ± 117 and 1608 ± 127; P=0.002 and 0.001), and β2AR (1104 ± 230 vs. 816 ± 73 and 837 ± 72; P=0.007 and 0.001).
- POTS IgG decreased phenylephrine-induced α1AR activation in 8/17 patients and increased isoproterenol-induced β1AR activation in 13/17 patients; 13/17 POTS IgG also increased contractility in isolated rat cremaster arterioles, which was reversed by α1AR blockade with phentolamine.
- Upright heart rate correlated with IgG-mediated β1AR activity (3 min P=0.0009; maximal P=0.0006) and α1AR activity (maximal P=0.039), but not with β2AR activity (P=0.11).
Methods
- Case-control functional study using serum IgG from 17 POTS patients (16 females; age 26 ± 9 years), 7 recurrent VVS patients (5 females; age 31 ± 9 years), and 11 healthy controls (10 females; age 31 ± 6 years) recruited from the SYSTEMA cohort in Malmö, Sweden.
- IgG was tested in cell-based assays for α1AR activation (FRET β-lactamase reporter in α1AR-NFAT-bla CHO-K1 cells) and β1AR/β2AR activation (cAMP Hunter eXpress GPCR assay in transfected CHO cells), with blockade by prazosin or propranolol, and in an isolated rat cremaster arteriole contractility assay with phentolamine.
- Group comparisons used Student’s t-test, one-way ANOVA with Tukey post hoc, Pearson’s χ2, and linear regression; autoantibody positivity was defined as above mean + 2SD or below mean − 2SD of controls.
Limitations
- The paper states that parasympathetic tonus was not assessed during head-up tilt and that possible autoantibodies against muscarinic receptors and/or the acetylcholine system were not investigated.
- The paper states that study groups were not strictly age matched, although the age difference was not significant.
- Evident from the text: the study has small group sizes (17 POTS, 7 VVS, 11 controls), and the authors note that the cremaster arteriolar bioassay is not suitable for large numbers of samples.
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54 Own result · 17 Own interpretation · 16 Own method · 15 Not checked yet · 2 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
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- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plainn = 17- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β2AR: POTS 1104 ± 230 vs. VVS 816 ± 73 and control 837 ± 72, P= 0.007 and 0.001, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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In the paper
“β1AR: POTS 1840 ± 186 vs. VVS 1578 ± 117 and control 1608 ± 127, P= 0.002 and 0.001, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaincorrelationaln = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plainn = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“α1AR: POTS 0.31 ± 0.07(SD) vs. VVS 0.24 ± 0.04 and control 0.23 ± 0.04, P= 0.029 and 0.004, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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In the paper
“None of these autoantibodies were found in the patients with VVS or healthy controls.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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In the paper
“Based on these direct assays, 6 of these 17 POTS patients (35%) harboured both α1AR- and β1AR-AAb (Table 2).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plainn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“As shown in Figure 3B, POTS IgG-induced contractility was largely returned to baseline level by addition of the α1AR blocker phentolamine (10 µM, from 88.9 ± 3.0% to 96.5 ± 2.1%, P= 0.0006).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thirteen of the 17 POTS patients were positive for an enhanced effect on isoproterenol-induced β1AR activation using a cut-off value of the mean + 2D from the control group (Figure 2F).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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In the paper
“A total of 13 among the 17 POTS patients demonstrated significantly increased contractility (Figure 3A).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaincorrelationaln = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“These data showed a heterogeneous response in which the majority with increased α1AR activity from the cell-based assay also demonstrated arteriolar contractile activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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In the paper
“The present study focused on the activity expected with these receptors; but identified a unique property of the studied IgG directed toward the α1AR which exerted allosteric effects characteristic of a partial agonist since its presence shifted the phenylephrine dosage response curve to the right.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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In the paper
“In the linear regression analysis, IgG-mediated β1AR activity was strongly correlated with both 3 min (P= 0.0009) and maximal upright heart rate (P= 0.0006), whereas the latter was also correlated with α1AR activity (P= 0.039) but not with β2AR activity (P= 0.11).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“When each individual data was plotted, 8 of the 17 POTS patients demonstrated an inhibitory effect on phenylephrine-induced α1AR activation using a cut-off value of the mean—2SD from the control group (Figure 2E).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
boosteddirectn = 8- Asserted: passes — The authors put it forward as true.
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In the paper
“there was no significant difference in catecholamine profile supine and 3-min HUT between POTS and VVS (see Supplementary material online, Table S1).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“The mean activities of α1AR, β1AR, and β2AR autoantibodies in 13 POTS patients were markedly suppressed by the α1AR blocker prazosin (10 µM, from 0.52 ± 0.06 to 0.46 ± 0.05, P= 0.0001) and β-blocker propranolol (1 µM, β1AR: from 1068 ± 233 to 821 ± 71, P= 0.0013; β2AR: from 1221 ± 164 to 988 ± 37, P= 0.0001) (Figure 1D–F).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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In the paper
“The VVS group reported a longer history of syncopal symptoms (P= 0.017), but the number of syncope episodes, proportions of characteristic precipitating symptoms, and self-reported dizziness on standing did not differ between POTS and VVS patients.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There was a significant difference in the mean contractile activity between the POTS group and control group (91.0 ± 3.1% vs. 96.5 ± 1.3%, P< 0.0001).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaincorrelationaln = 8- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
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In the paper
“Phentolamine had no significant impact on control IgG activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plainn = 6- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Overall, all POTS subjects had at least one positive test.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plainn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaincorrelationaln = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, the isoproterenol response curve was significantly shifted to the left, demonstrating an enhanced β1AR response with β1AR autoantibodies (Figure 2B).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
boosteddirectn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plainn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“Eight subjects with no α1AR direct activity from the cell-based assay also demonstrated positive contractile activity, while three subjects with positive α1AR activity from the cell-based assay demonstrated no arteriolar contractile activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
boostedn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“All patients in the POTS group had documented persistent increase in heart rate >30 bpm vs. supine during head-up-tilt with reproduction of typical orthostatic intolerance symptoms.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
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In the paper
“In contrast to our initial publication,8 nearly half of the POTS subjects had direct activation of the α1AR autoantibody activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The VVS group reported a longer history of syncopal symptoms (P= 0.017), but the number of syncope episodes, proportions of characteristic precipitating symptoms, and self-reported dizziness on standing did not differ between POTS and VVS patients.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In the present study, approximately two-thirds activated β1/2AR in cell-based assays.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Control IgG showed minimal modulating effects.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the linear regression analysis, IgG-mediated β1AR activity was strongly correlated with both 3 min (P= 0.0009) and maximal upright heart rate (P= 0.0006), whereas the latter was also correlated with α1AR activity (P= 0.039) but not with β2AR activity (P= 0.11).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean activities of α1AR, β1AR, and β2AR autoantibodies in 13 POTS patients were markedly suppressed by the α1AR blocker prazosin (10 µM, from 0.52 ± 0.06 to 0.46 ± 0.05, P= 0.0001) and β-blocker propranolol (1 µM, β1AR: from 1068 ± 233 to 821 ± 71, P= 0.0013; β2AR: from 1221 ± 164 to 988 ± 37, P= 0.0001) (Figure 1D–F).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The VVS group reported a longer history of syncopal symptoms (P= 0.017), but the number of syncope episodes, proportions of characteristic precipitating symptoms, and self-reported dizziness on standing did not differ between POTS and VVS patients.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean activities of α1AR, β1AR, and β2AR autoantibodies in 13 POTS patients were markedly suppressed by the α1AR blocker prazosin (10 µM, from 0.52 ± 0.06 to 0.46 ± 0.05, P= 0.0001) and β-blocker propranolol (1 µM, β1AR: from 1068 ± 233 to 821 ± 71, P= 0.0013; β2AR: from 1221 ± 164 to 988 ± 37, P= 0.0001) (Figure 1D–F).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The control subjects failed to produce any significant vasoactivity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plainn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No significant effect of these blockers was observed in the control group.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight subjects with no α1AR direct activity from the cell-based assay also demonstrated positive contractile activity, while three subjects with positive α1AR activity from the cell-based assay demonstrated no arteriolar contractile activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
boostedcorrelationaln = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“POTS-related syncope differs from classic vasovagal syncope (VVS), as the underlying symptoms are present constantly with occasional syncope associated with a preceding tachycardia and associated adrenergic symptoms. In contrast, VVS typically features episodic syncope and asymptomatic periods between attacks.1,4,7”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [1] Benarroch, 2012, Postural tachycardia syndrome: a heterogeneous and multifactorial disorder, Mayo Clin Proc source
- Not checked yetcites [4] Moya, 2009, Guidelines for the diagnosis and management of syncope (version 2009), Eur Heart J source
- Not checked yetcites [7] Fedorowski, 2013, Syndromes of orthostatic intolerance: a hidden danger, J Intern Med source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“but its aetiology remains unknown.3–5”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [3] Low, 1995, Postural tachycardia syndrome (POTS), Neurology
- Not checked yetcites [4] Moya, 2009, Guidelines for the diagnosis and management of syncope (version 2009), Eur Heart J source
- Not checked yetcites [5] Brignole, 2000, New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study, Europace source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These autoantibodies appear to function as partial agonists and the absence of measurable direct activation of the transfected receptors in vitro in the absence of their normal ligand does not exclude their presence.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The autoantibodies may also exert an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no significant difference in BP response during the first 3 min of head-up tilt in the POTS compared with VVS and controls”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The autoantibodies may also exert an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Serum from patients diagnosed with postural tachycardia syndrome contains circulating autoantibodies with a direct stimulatory effect on adrenergic receptors.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These autoantibodies appear to function as partial agonists and the absence of measurable direct activation of the transfected receptors in vitro in the absence of their normal ligand does not exclude their presence.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The α1AR activity in our previous study was assayed using IgG in an arteriolar assay and not the present cell-based assay.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lower but still significant relationship of the allosterically mediated inhibitory action of the α1AR response would secondarily lead to the increase in heart rate by reflexly increasing circulating catecholamines.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
In the paper
“Recognition that circulating autoantibodies interact with G protein-coupled receptor targets and modify the autonomic system has led our group to identify AAb to the β2AR and M3 muscarinic acetylcholine receptor in a group of subjects with idiopathic orthostatic hypotension.15”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [15] Li, 2012, Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism, Hypertension source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data confirm a strong relationship between adrenergic autoantibodies and POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Conclusion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study has an important limitation as the parasympathetic tonus was not assessed during HUT, and possible autoantibodies against muscarinic receptors and/or acetylcholine system were not investigated.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“We have recently demonstrated an exaggerated catecholamine response in postural tachycardia among patients with syncope and dysautonomic cardiovascular response to orthostasis.19”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [19] Nilsson, 2015, Orthostatic changes in hemodynamics and cardiovascular biomarkers in dysautonomic patients, PLoS ONE source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, some subjects who do not formally meet the diagnostic criteria of POTS may have partial presentation of such autoantibodies.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We believe that the present study helps affirm our concept that common cardiovascular dysautonomias may express a spectrum of autoantibodies, which contribute to a variety of clinical manifestations.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From our studies, subjects with recurrent VVS and normal orthostatic tolerance would not be likely candidates for inclusion in this grouping.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study has an important limitation as the parasympathetic tonus was not assessed during HUT, and possible autoantibodies against muscarinic receptors and/or acetylcholine system were not investigated.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The marked presence of either or both α1AR and β1/2AR autoantibodies with their potent allosteric impact on the relevant orthosteric ligands provides an appealing framework to support an autoimmune pathophysiology of POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: There is a paucity of concrete evidence for other pathophysiological bases for POTS for the vast majority of patients.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that under these conditions, the primary action of the autoantibodies is not an orthosteric direct activation or inhibition of the receptor but rather modulation of the activity and action of the ligand norepinephrine/epinephrine that normally is involved in the particular receptor transduction.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These contrasting effects provide an appealing explanation for the cardiovascular effects associated with upright posture in those so afflicted.1,8”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We have introduced a new direct assay to measure α1AR activity, which although similar in principle to the assay for β1/2AR in transfected cells was only positive in half of the POTS patients compared with the more demanding previous bioassay that measured contractility in the cremaster arterioles in vitro.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 28
- Probably not a substantial claim. 18
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β1/2AR autoantibody activity was increased in POTS but not in VVS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the linear regression analysis, IgG-mediated β1AR activity was strongly correlated with both 3 min (P= 0.0009) and maximal upright heart rate (P= 0.0006), whereas the latter was also correlated with α1AR activity (P= 0.039) but not with β2AR activity (P= 0.11).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither shift was observed using control IgG.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We have demonstrated that serum from subjects with POTS contains circulating autoantibodies, some with a direct stimulatory effect on adrenergic receptors.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no significant difference between the latter two groups.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a significant decrease in phenylephrine-induced α1AR activation with POTS IgG (0.13 ± 0.02) compared with phenylephrine alone (0.18 ± 0.03, P< 0.0036) or IgG from normal controls (0.17 ± 0.02, P< 0.0005) (Figure 2C).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither SBP nor DBP were correlated with adrenergic receptor stimulation.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The VVS group reported a longer history of syncopal symptoms (P= 0.017), but the number of syncope episodes, proportions of characteristic precipitating symptoms, and self-reported dizziness on standing did not differ between POTS and VVS patients.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The isoproterenol-stimulated β1AR activation, on the other hand, was significantly increased with POTS IgG (1835 ± 309) compared with isoproterenol alone (1479 ± 86, P< 0.037) or IgG from normal controls (1508 ± 80, P< 0.032) (Figure 2D).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was some overlap for the α1AR and considerable overlap for the β1AR with the other tests (Table 2).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the primary objective, we found that antiadrenergic α1AR autoantibody activity was evident in POTS, while the VVS subjects were not different from normal subjects.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the presence of POTS IgG, the phenylephrine response curve was shifted to the right, demonstrating a decreased α1AR response (Figure 2A).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
boosteddirectn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A majority also exerted an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As previously reported,8 these data confirmed the active α1AR autoantibodies inhibited the phenylephrine response and shifted the phenylephrine dosage response curve to the right.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, β1AR autoantibodies enhanced the isoproterenol response and most importantly shifted the isoproterenol dosage response curves to the left, confirming our previous observations.8”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the β1AR effect was just the opposite and shifted the β1AR agonist dosage response curve to the left.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since the pathophysiological basis for POTS is unclear, therapeutic interventions are empirical.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This procedure was approved by the Oklahoma University Health Sciences Center Institutional Animal Care and Use Committee.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Isolated cremaster arteriole assay
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“A number of treatment options have been proposed in POTS but their efficacy in the more severe forms is limited and often questioned.2,7”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
- Not checked yetcites [7] Fedorowski, 2013, Syndromes of orthostatic intolerance: a hidden danger, J Intern Med source
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All samples were assayed in triplicate.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Cell-based α1AR assay
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Receipt and assay of these de-identified samples was approved by the University of Oklahoma Health Sciences Center Institutional Review Board.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Sample preparation
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean age for the POTS patients was not significantly different from those with VVS and control subjects.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In order to ascertain the accuracy of diagnoses, the digital test records were subsequently inspected off-line using Nexfin@PC (BMEYE, Amsterdam, the Netherlands), dedicated software provided by the manufacturer.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Diagnostic criteria of postural tachycardia syndrome and classic vasovagal syncope
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Li et al. recently reported that activating autoantibodies (AAb) to the α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR) might play a pathophysiological role in POTS.8”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
hedgedconditionaln = 7- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Negative (buffer) and positive (phenylephrine) controls were included in each assay.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Cell-based α1AR assay
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Its onset may follow an acute infection or vaccination but more commonly appears without antecedent causative events.2,6”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
- Not checked yetcites [6] Brinth, 2015, Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus, Vaccine source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the SYSTEMA cohort, we randomly selected 17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years), and 7 with recurrent VVS (5 females; age: 31 ± 9 years).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
plainn = 17- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The Regional Ethical Review Board in Lund, Sweden approved the study protocol (ref no 82/2008), and all study participants gave their written informed consent including serum analyses.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Examination protocol
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These and possibly other yet-to-be identified immunoglobulins with different target epitopes may exert varying biological effects in particular patients, which may explain different constellations of symptoms in POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the SYSTEMA cohort, we randomly selected 17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years), and 7 with recurrent VVS (5 females; age: 31 ± 9 years).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
plainn = 17- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, the study groups were not strictly age matched, although the age difference was not significant.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The catecholamine surge may be seen as a compensatory mechanism to override the α1AR malfunction associated with the proposed autoimmune blockade as present in POTS patients but this explanation is unlikely in those with recurrent VVS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This report more than doubles the number of our previous observations, and focuses on a tightly characterized group of patients and controls.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diagnostic criteria based on measuring the autoantibodies' impact on an allosteric-mediated receptor response to the natural ligand may provide a more favourable estimate of autoantibody involvement in the complex pathophysiology of POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This cremaster arteriolar bioassay is not suitable for use in large numbers of samples and the specific cell-based assays are an improvement with regard to numbers.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It seems apparent that the high percentage of POTS subjects examined by our group present with an apparent autoimmune diathesis that supports the concept that these autoantibodies play important role in the pathophysiology of this entity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: There is a paucity of concrete evidence for other pathophysiological bases for POTS for the vast majority of patients.
In the paper
“The vagal drive may have an important implication in related POTS symptomatology.20”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
What the sources say
- Not checked yetcites [20] Yoshida, 2014, Variant cardiovascular regulation in children with postural tachycardia syndrome, Pediatr Int source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Both POTS and IST share abnormal sinus tachycardia tendency, and differ in regard to resting heart rate control that is usually preserved in POTS but not in IST.2”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This spectrum would certainly range from subclinical to overt expressions that may overlap with other entities such as inappropriate sinus tachycardia (IST), where circulating antibodies against cardiac β-receptors have been previously reported.18”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [18] Chiale, 2006, Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta andrenergic receptors, Heart Rhythm source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
“we planned to examine the AAb profile of a larger, well-characterized, and representative cohort of patients with POTS from an independent European institution whose selection was completely separate from the originating laboratory.”
The paper relies on this without support.
There is a paucity of concrete evidence for other pathophysiological bases for POTS for the vast majority of patients.
“Although it is likely that POTS has multiple causes, there has been a paucity of concrete evidence for other pathophysiological bases for an underlying pathophysiology to date for the vast majority of patients.”
The paper relies on this without support.
The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
“Immunoglobulin G (0.05 mg/mL) from each subject with POTS and 8 controls were tested for α1AR autoantibody-mediated contractile activity using an isolated rat cremaster arteriole assay.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Although altered GPCR activity in people with POTS has been observed (Fedorowski et al., 2017”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Fedorowski et al., 2017
In the citing paper
“Serum immunoglobulins isolated from POTS patients have been reported to act as partial agonists to both α- and β-adrenergic receptors in vitro (Fedorowski et al., 2017; Li et al., 2014), a finding independently confirmed by several other groups (Vernino and Stiles, 2018) and expanded to include a wider range of G-protein coupled receptors (GPCRs) as targets (Kharraziha et al., 2020).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Fedorowski et al., 2017
In the citing paper
“Higher levels of autoantibodies against beta-1 and beta-2 adrenoreceptors have been detected in POTS patients versus healthy controls in serologic studies (32, 44).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“This group also demonstrated that autoantibody affinity toward beta-receptors positively correlated with a greater degree of orthostatic tachycardia (44).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“Fedorowski et al. (44) demonstrated that these autoantibodies, in addition to acting like a direct beta-agonist, can also upregulate sympathetic nervous activity through allosteric interactions with the beta-receptors.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“Circulating antibodies to α1-and β-adrenergic receptors and cardiac lipid raft-associated proteins have also been discovered in POTS (Fedorowski et al., 2017;Wang et al., 2013;Li et al., 2014).”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Fedorowski et al., 2017
In the citing paper
“A specific focus was given cardiovascular G-protein-coupled membrane complexes, such as adrenergic, muscarinic and angiotensin II type-1 receptors The symptoms of POTS, especially [43,45] (Fig. 1).”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [45]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
“17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years)”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
“| Sex M/F | 2/15 | 2/5 | 1/10 | 0.55/0.98 |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
“A majority also exerted an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
“| Total | 8/17 | 8/17 | 11/17 | 13/17 | 12/17 |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
“POTS (16 females; age, 26 ± 9 years)”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
“| Age | 25 ± 7 | 31 ± 9 | 31 ± 6 | 0.17/0.063 |”
Citations
Cites
Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040
Self-citationFreeman, R., Wieling, W., Axelrod, F. B., Benditt, D. G., Benarroch, E., Biaggioni, I., Cheshire, W. P., Chelimsky, T., Cortelli, P., Gibbons, C. H., et al. (2011) · Autonomic Neuroscience · doi:10.1016/j.autneu.2011.02.004 · Cited by 1,243
Sheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013
Self-citationPostural tachycardia syndrome: a heterogeneous and multifactorial disorder
Benarroch, E. E. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2012.08.013 · Cited by 370 · cited 4×
“It often leads to debilitating symptoms and uncertain long-term prognosis.(1) A number of treatment options have been proposed in POTS but their efficacy in the more severe forms is limited and often questioned.”
BackgroundInfluentialHemodynamic Response to the Upright Posture
Smith, J. J., Porth, C. M., & Erickson, M. (1994) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1994.tb04977.x · Cited by 320 · cited 1×
“pulse increase ,30 bpm and absence of orthostatic hypotension).(10,11) All the patients and controls were recruited from the same community of Malmö or neighbouring municipalities in Skåne Region, Southern Sweden.”
BackgroundBartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · cited 1×
“The head-up tilt (HUT) test for SYSTEMA patients was performed according to the Italian protocol.(12) The tilt table was raised at constant speed to 708 in 18 s, and had the same lowering time.”
MethodPostural tachycardia syndrome (POTS)
Lamotte, G., & Low, P. A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-85492-4.00118-6 · Cited by 301
Guía de práctica clínica para el diagnóstico y manejo del síncope (versión 2009)
Moya‐Mitjans, À., Sutton, R., Ammirati, F., Blanc, J., Brignole, M., Dahm, J. B., Deharo, J., Gajek, J. J., Gjesdal, K., Krahn, A. D., et al. (2009) · Revista Española de Cardiología (English Edition) · doi:10.1016/s1885-5857(09)73541-8 · Cited by 277
Self-citationAutoimmune Basis for Postural Tachycardia Syndrome
Li, H., Yu, X., Liles, C., Khan, M., Vanderlinde‐Wood, M., Galloway, A., Zillner, C., Benbrook, A., Reim, S., Collier, D., et al. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000755 · Cited by 255 · cited 12×
“Immunoglobulin G-mediated b1AR and b2AR activation of cAMP production in transfected CHO cells (with either b1AR or b2AR stimulation) was measured using the cAMP Hunter eXpress GPCR Assay kit (DiscoveRx) as described.(8,15) Briefly, b1AR- or b2AR-CHO cells were dispensed into 96-well plates and incubated overnight.”
BackgroundMethodResultInfluentialSelf-citation
Cited by
Sorted by citations
2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951
Self-citationAutonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies
Dani, M., Dirksen, A., Taraborrelli, P., Torocastro, M., Panagopoulos, D., Sutton, R., & Lim, P. B. (2020) · Clinical Medicine · doi:10.7861/clinmed.2020-0896 · Cited by 769
Self-citation2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya‐Mitjans, À., de Lange, F. J., Deharo, J., Elliot, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martiın, A., et al. (2018) · Kardiologia Polska · doi:10.5603/kp.2018.0161 · Cited by 475
Self-citationPostural orthostatic tachycardia syndrome: clinical presentation, aetiology and management
Fedorowski, A. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12852 · Cited by 352
Self-citationVernino, S., Bourne, K. M., Stiles, L. E., Grubb, B. P., Fedorowski, A., Stewart, J. M., Arnold, A. C., Pace, L. A., Axelsson, J., Boris, J. R., et al. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102828 · Cited by 304
Self-citation
Metadata
- Authors
- Fedorowski, A., Li, H., Yu, X., Koelsch, K. A., Harris, V. M., Liles, C., Murphy, T. A., Quadri, S. M. S., Scofield, R. H., Sutton, R., Melander, O., & Kem, D. C.
- Affiliations
- Lund University (SE)
- University of Oklahoma Health Sciences Center (US)
- Oklahoma Medical Research Foundation (US)
- Imperial College London (GB)
- Corresponding author
- Fedorowski, Artur
- ORCID
- Venue
- EP Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-10-04
- Volume
- 19
- Issue
- 7
- Pages
- 1211-1219
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- PMC
- PMC5834103
- OpenAlex
- W2528071726
- Semantic Scholar
- 31fdba9a6b101b72fdc3c4780b2b82249e111255
- Cited by
- 151
- References
- 22
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 23 · 2022: 24 · 2021: 18 · 2020: 21 · 2019: 11 · 2018: 14 · 2017: 8
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- EP Europace (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- European Society of Cardiology
- Lunds Universitet
- Medical Research Council
- National Heart, Lung, and Blood Institute (R01HL128393, R56HL128393)
- National Institute of General Medical Sciences (U54GM104938)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- postural orthostatic tachycardia syndrome, autoantibodies, adrenergic receptors, alpha1-adrenoceptors, beta1-adrenergic receptor, beta2-adrenergic receptor, vasovagal syncope, orthostatic intolerance, autonomic dysfunction
- MeSH terms
- Abdominal Muscles, Adolescent, Adult, Animals, Arterioles, Autoantibodies, Cricetulus, Dose-Response Relationship, Drug, Female, Humans, Immunoglobulin G, Male, Transfection, Vasoconstriction, Autoimmunity, Case-Control Studies, CHO Cells, Receptors, Adrenergic, alpha-1, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Rats, Postural Orthostatic Tachycardia Syndrome, Young Adult, Adrenergic alpha-1 Receptor Agonists, Adrenergic beta-1 Receptor Agonists, Adrenergic beta-2 Receptor Agonists, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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