Relevance of CellTrend results for treatment

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As most of you will already know, CellTrend offers a test panel for various autoantibodies, including autoantibodies against the adrenergic receptors, and autoantibodies against the muscarinic cholinergic receptors. This is important, as various studies have shown the presence of high levels of these autoantibodies in ME/CFS, POTS and long covid, suggesting a possible autoimmune basis for these conditions. In fact, this finding may justify the employment of immune therapies such as IVIG, plasmapheresis or Rituximab.

Nevertheless, I wonder whether the presence of these autoantibodies is the cause of our symptoms (i.e. they are centrally pathogenic) or whether they simply are a bystander effect of the primary disease process. To the best of my knowledge, this important issue has not been resolved so far in the literature (please correct me if I am wrong).

In view of this, I would like to know if your doctors use the CellTrend results as a guide for treatment. In particular, is there anyone who has obtained good results using immune therapy to target these specific autoantibodies in absence of other autoimmune conditions?
 

Pyrrhus

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Pyrrhus

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You may also be interested in the following discussions:

Here is the classic 2015 paper by Carmen Scheibenbogen that discovered autonomic auto-antibodies in ME:

Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome (2015)
https://forums.phoenixrising.me/thr...inergic-receptors-in-patients-with-cfs.40109/
This paper was the first to report antibodies that target three types of neurotransmitter receptors on autonomic nerves, in 29.5% of patients with ME. The paper suggested that when these antibodies were depleted by Rituximab treatment, patients experienced an improvement in symptoms.

And here is an updated paper by Carmen Scheibenbogen that used the CellTrend test:

Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2021)
https://forums.phoenixrising.me/thr...isability-in-me-cfs-freitag-et-al-2021.87566/
This paper looked for correlations between certain antibodies and symptoms in ME. They found that levels of these certain antibodies significantly correlated with key symptoms of fatigue and muscle pain in patients with infection-triggered onset, but not in patients without an infection-triggered onset. They further suggest that specific antibodies might show some correlation with specific symptoms.
 

Pyrrhus

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And here are two studies from Carmen Scheibenbogen that tried to remove these antibodies by a therapy called "immunoabsorption".

Immunoabsorption is one type of plasmapheresis that removes many of the patient's antibodies in a somewhat indiscriminate way. Since immunoabsorption temporarily depletes the patient's antibodies, the investigators gave all patients IVIG at the end of each week-long immunoabsorption treatment, in order to restore their antibody levels to normal.

Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME (2018)
https://forums.phoenixrising.me/thr...renergic-receptor-antibodies-in-cfs-me.58277/
This small pilot study used immunoabsorption therapy on 10 ME patients who had antibodies to a specific autonomic receptor. The therapy successfully decreased the level of antibodies in 9 of 10 patients. 7 of those 9 patients reported a rapid improvement of symptoms. 3 of the 7 reported that their improvement lasted for at least a year, but the rest of the 7 relapsed within a year.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption (2020)
https://forums.phoenixrising.me/thr...mmunoadsorption-published-30-july-2020.80959/
In this follow-up study, 5 of the patients in the 2018 pilot study who had reported improvement of symptoms, but then relapsed, were re-treated about two years later with a slightly modified treatment schedule. 4 of the 5 reported improvement of symptoms again, but one didn't. The improvement of symptoms lasted 6-12 months. The authors suggest that regular immunoabsorption therapy might be a treatment, but not cure, of ME.
 
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elvira

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I’d really like to know this too! If there are any case reports... The immunoadsorption study is promising, showing these antibodies really do cause a lot of trouble!
 
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@Pyrrhus , thanks for the references. There is also an interesting paper by Li et al. (2019) where the authors develop the first animal model linking adrenergic autoantibodies to POTS. Although the autoantibodies are functional in this model, it is unclear to what extent the findings of Li et al. (2019) can be extended to the patient population with POTS.

https://pubmed.ncbi.nlm.nih.gov/31547749/
 

Pyrrhus

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There is also an interesting paper by Li et al. (2019) where the authors develop the first animal model linking adrenergic autoantibodies to POTS.
Thanks for sharing that interesting article!

You may also be interested in these discussions:

Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies (Gunning et al., 2021)
https://forums.phoenixrising.me/thr...ptor-autoantibodies-gunning-et-al-2021.83073/

Antiadrenergic autoimmunity in postural tachycardia syndrome (Fedorowski et al., 2016)
https://forums.phoenixrising.me/thr...ycardia-syndrome-fedorowski-et-al-2016.47655/
 

halcyon

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Nevertheless, I wonder whether the presence of these autoantibodies is the cause of our symptoms (i.e. they are centrally pathogenic) or whether they simply are a bystander effect of the primary disease process. To the best of my knowledge, this important issue has not been resolved so far in the literature (please correct me if I am wrong).
There is an unfortunate third option: non-specific binding. The putative autoantibodies may not be anything at all and instead could just be promiscuous antibodies having fun in an ELISA well, a phenomenon made more likely by the presence of increased immunoglobulin concentration, or blood that has been exposed to sufficient heat.

A fourth option is that the antibodies could be real, but might show up in similar statistical amounts in healthy people.

In view of this, I would like to know if your doctors use the CellTrend results as a guide for treatment. In particular, is there anyone who has obtained good results using immune therapy to target these specific autoantibodies in absence of other autoimmune conditions?
No, my well-known doctor at a well-known institution does not use this test at all, and left me with the impression that option four above is the reason why.
 

elvira

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There is an unfortunate third option: non-specific binding. The putative autoantibodies may not be anything at all and instead could just be promiscuous antibodies having fun in an ELISA well, a phenomenon made more likely by the presence of increased immunoglobulin concentration, or blood that has been exposed to sufficient heat.

A fourth option is that the antibodies could be real, but might show up in similar statistical amounts in healthy people.


No, my well-known doctor at a well-known institution does not use this test at all, and left me with the impression that option four above is the reason why.
Jonas Bergquists autoantibody study for OMF included healthy controls and there was a big difference between that cohort and ME-patients. I think 20% of healthy people had the tested AABs while 70-80% of the ME cohort had them.
 

Pyrrhus

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Does anyone know if Dr Scheibenbogen sees patients ... or if there's another clinician who's across the CellTrend panels who sees patients? I did the POTS panel and have a number of elevated autoantobody readings, but wonder who I can talk to about possible treatments.
 
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The treatment objective for those auto-antibodies would most likely be BC007. Which is not available.
Yes, BC007 may be a possibility. Options currently avaliable include IVIG, plasmapheresis/immunoadsorption or immunosupressant drugs (e.g. rituximab). However, these treatments only would be effective if the GPCR autoantibodies are centrally pathogenic (i.e. they are causing the symptoms), which to the best of my knowledge has not been confirmed so far in the literature.
 
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@stephano75, a recent study finds no differences in GPCR autoantibody concentrations between patients with POTS and healthy controls when using CellTrend tests (ELISA).

https://ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.059971

In view of this I think that the results of the Celltrend POTS panel should be treated with caution.
Thanks @Castorp. Agree re treated with caution.
From my perspective (CFS for 25 years, and have now reached a point of being relatively functional), I'd still love to have a conversation with a clinician who's across the field. (Doubtless someone like Dr Scheibenbogen would be interested in that paper too.)
When I see Long Covid 'clinics' gravely talking about a 'multidiscplinary approach' ... but note it still means psychological approaches and variations on GET, it's clear they have learnt slightly less than absolutely nothing about post-viral illness over the past few decades (maybe more like the past half century). And of course nobody really knows for sure why plasmapheresis/immunoadsorption is helpful (to the extent that it is), but again talking with someone who's interested in how and why immune dysregulation/possible auto-immune issues contribute to ME/CFS would be illuminating, and would help inform future treatment decisions.

Cheers,
Stephen
 

Husband of

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There is an unfortunate third option: non-specific binding. The putative autoantibodies may not be anything at all and instead could just be promiscuous antibodies having fun in an ELISA well, a phenomenon made more likely by the presence of increased immunoglobulin concentration, or blood that has been exposed to sufficient heat.

A fourth option is that the antibodies could be real, but might show up in similar statistical amounts in healthy people.


No, my well-known doctor at a well-known institution does not use this test at all, and left me with the impression that option four above is the reason why.
Do you have capacity to explain/elaborate a bit on that third option?

In your view , is any light shed on the fourth option by the response of the patients in the small study posted by pyrrhus above (Immunoadsorption to remove ß2 adrenergic receptor antibodies).?