Detection of G Protein-Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology (2022) Hall et al

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

(the title is a bit misleading, read the whole abstract)
Main author is Dr Satish Raj from Calgary.

Abstract
Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein-coupled receptors between patients with POTS and healthy controls.

Methods: Sera were collected from 116 patients with POTS (91% female; mean age, 29 years) and 81 healthy controls (84% female; mean age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay.

Results: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls.

Conclusion: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay-derived autoantibody concentrations to cardiovascular G protein-coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.

Abstract only here

 

Addendum: I believe I was a subject for this study and I assume this is a first paper and there is a possibility that follow up papers may publish from that same cohort.

 

That’s hilarious.

 

Full open access text here
https://www.ahajournals.org/doi/epdf/10.1161/CIRCULATIONAHA.122.059971

This study has been planned for a number of years and was part funded by Dysautonomia International. In simple terms they wanted to find out if the CellTrend test was any good or not. Artur Fedorowski from Sweden and one of the authors of this paper gave a presentation about the work at the 2021 Dysautonomia International Conference and I noted the summary then.

https://twitter.com/user/status/1416206025087012867


I believe Dr Satish Raj, the other main author on this paper is very highly respected in the POTS research and patient community.

This supports the previous ME/CFS finding by Jonas Berquist et al that the CellTrend test for ME/CFS is no good for individual diagnostics, only perhaps interesting for group to group comparisons in a research setting.

Back in 2018, Berlin Cures published a paper showing ELISA with human antibodies (such as CellTrend) was not a good test in comparison to animal antibodies.
Paper : Difference between beta1-adrenoceptor autoantibodies of human and animal origin-Limitations detecting beta1-adrenoceptor autoantibodies using peptide based ELISA technology
https://pubmed.ncbi.nlm.nih.gov/29425252/

 

If Berlin Cures are right the test is probably no use in any situation - i.e., if it does not pick up antibodies reliably.

I suspect it is more likely that the antibodies are not there in any meaningful sense.

 

Fedorowski (one of the authors) flogged this for a while, when it became clearer that it wasn't a useful test someone (CellTrend?) put forward a grouping of CellTrend AAB results that still promised to be diagnostic and I recall him discussing plans to test that. This paper refers to analysis against AAB groupings that still do not show a diagnostic yield high enough to be clinically significant.

The paper references the importance of functional cell-based assays (to detect AAB activity - prior Raj work) but I thought there were also some promising alternative tests for more reliable detection too - I expect we'll get some updates on these at the Dysautonomia conference in July.

 

Is it logical to say then that autoantibodies for cell receptors in ME patients at Cell Trend is likely to be problematic as well? Does it invalidate the work published from Germany?

 

I will have to replay that, I could not watch any of the morning presentations because it was too darn early for my time zone.