AAB to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction, Disability in ME/CFS, Scheibenbogen, 2021

Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Scheibenbogen et al

Abstract
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous dysfunction. ME/CFS is triggered by an infection in the majority of patients. Initial evidence for a potential role of natural regulatory autoantibodies (AAB) to beta-adrenergic (AdR) and muscarinic acetylcholine receptors (M-AChR) in ME/CFS patients comes from a few studies. Methods: Here, we analyzed the correlations of symptom severity with levels of AAB to vasoregulative AdR, AChR and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) receptor in a Berlin cohort of ME/CFS patients (n = 116) by ELISA. The severity of disease, symptoms and autonomic dysfunction were assessed by questionnaires.

Results: We found levels of most AABs significantly correlated with key symptoms of fatigue and muscle pain in patients with infection-triggered onset. The severity of cognitive impairment correlated with AT1-R- and ETA-R-AAB and severity of gastrointestinal symptoms with alpha1/2-AdR-AAB. In contrast, the patients with non-infection-triggered ME/CFS showed fewer and other correlations.

Conclusion: Correlations of specific AAB against G-protein-coupled receptors (GPCR) with symptoms provide evidence for a role of these AAB or respective receptor pathways in disease pathomechanism. View Full-Text

https://www.mdpi.com/2077-0383/10/16/3675

 

"In contrast, the patients with non-infection-triggered ME/CFS showed fewer and other correlations"

How is it possible to distinguish between infection and non infection triggered ? Self report cannot identify underlying pathophysiology. This unaddressed assumption could have a major impact on the conclusions being drawn.

 

Note that this study didn't utilise any healthy or non-ME/CFS control groups, so none of the findings are generalisable as biomarkers.

I still find the hypothesis really intriguing, but we are going to need more evidence...

This is a good point. There weren't really any major differences between the two groups, despite the claims.

 

This is certainly true. And also people could have subclinical infections that are triggering it, or mild infections they don't really remember years later when they finally get diagnosed.

 

Yet they found correlations distinguishing the infective vs non CFS groups and assuming for the moment this is not itself due to bias, which one has to entertain as a possible explanation, then you have to wonder how they chose their cohorts, who really chose them and on what criteria.

From a previous paper, their ref #25
Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset.

This is an attempt to subtype which I think is important but the method is risking tautology. If the patients who have AABs are correlated with infection onset retrospectively then there is the potential for bias.

I agree neither self reporting or retrospective analysis are rigorous. I think one has to do this kind of investigation to devise an hypothesis, as it were one cannot make an omelette without breaking eggs but then testing the hypothesis has to be beyond cognitive interference. So I would call this investigative but not definitive.

To be definitive, I dont know, could they use a quantifiable metric like antibodies to the viruses in question like the +ve IgG result I had for EBV (1982) in 2015?

Even if they cant empirically prove an association with infection, surely AABs to AdR and AChR could themselves be used as a criterion for defining a subtype?