What Causes ME/CFS: The Role of the Dysfunctional Immune System and Viral Infections, 2022, Bansal, Carding et al

[Tom Kindlon]

Free:
https://maplespub.com/article/what-...functional-immune-system-and-viral-infections

Review Article | Open Access2022|Volume 3|Issue 2|
https://doi.orG/10.37191/Mapsci-2582-6549-3(2)-033
What Causes ME/CFS: The Role of the Dysfunctional Immune System and Viral Infections
Amolak S Bansal1*, Aletta D Kraneveld2, Elisa Oltra3 and Simon Carding4

1Consultant in Immunology, Allergy and CFS/ME, Spire Bushey Hospital, Watford, UK

2Chair Interdisciplinary Translational Pharmacology, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht the Netherlands

3Department of Pathology, Faculty of Medicine and Health Sciences, Catholic University of Valencia, Valencia, Spain

4Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK and Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK

*Corresponding Author: Amolak S Bansal,Consultant in Immunology, Allergy and CFS/ME, Spire Bushey Hospital, Watford, UK.

ReceivedAug 12, 2022 RevisedAug 22, 2022 AcceptedAug 29, 2022 Published
Sep 16, 2022

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains an enigmatic highly disabling and complex long-term condition with a wide range of aetiologies and symptoms.

A viral onset is commonly mentioned by patients and several bodily systems are ultimately disturbed.

The parallel with long-covid is clear. However, immune dysregulation with impaired NK cell dysfunction and tendency to novel autoimmunity have been frequently reported.

These may contribute to reactivation of previous acquired viruses/retrovirusesaccompanied by impaired endocrine regulation and mitochondrial energy generation.

The unpredictable nature of seemingly unconnected and diverse symptoms that are poorly responsive to several allopathic and alternative therapies then contributes to an escalation of the illness with secondary dysfunction of multiple other systems.

Treatment of established ME/CFS is therefore difficult and requires multi-specialty input addressing each of the areas affected by the illness.

Keywords
Myalgicencephalomyelitis/chronic fatigue syndrome (ME/CFS), Immune system, Viruses, Retroviruses, Cytokines, NK cells, Mitochondria

 

[Hutan]

It's not the worst review I've seen, but you know that's a very low bar. Sorry, but this is disappointing, it seems superficial. It doesn't change my view of Bansal as teetering on the edge of BPS thinking.

Collectively, variable patterns in immune dysfunction may explain the specific combinations of symptoms experienced by patients and their likelihood of improvement. Unravelling the details of these changes will not only help patients understand the nature of their illness and its multiple symptoms, but also provide important clues as to how it is best treated.

What is that actually saying? That immune dysfunction might be involved, but it might not? And if we knew what was causing the symptoms, that would help patients understand their illness and might provide clues as to how to treat it? Well, yes...

More recently attention has been focused on correlating psychological variables and sleep disturbance with cytokine levels [36]. This suggested an association between executive function and IL-1 and IL-6, interpersonal function and IL-6 and TNF-α and sleep with IL1, IL2, IL6 and TNFa [36].

There needed to be a lot more critical thinking and analysis, rather than a reporting of results. It's not helpful to mix up results from studies that are clearly flawed with ones that might be useful.

Several studies have sought to identify diagnostic biomarkers for ME/CFS, with varying results. Using whole blood gene expression in 29 adolescent ME/CFS patients [10] found that 176 genes were differentially expressed, including CD79a, which is involved in B cell differentiation, activation and signaling; Tumor necrosis factor receptor superfamily 13C, which is involved in B cell homeostasis; and FLT3 (fms-related tyrosine kinase 3) which has effects on numerous aspects of the immune system including B and pro B cell survival, proliferation, differentiation and responses to cytokines. Collectively, these findings suggest that abnormal B cell differentiation and survival is related to ME/CFS and linked to an altered hypothalamus–pituitary-adrenal (HPA) axis.

The reference for this is
10. Nguyen CB, Alsøe L, Lindvall JM, Sulheim D, Fagermoen E, Winger A, Kaarbø M,et al. Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. J Transl Med. 2017;15(1):1-21.PubMed | CrossRef
I'd like to have a look at that study as it's not obvious to me from the paragraph how, collectively, the findings suggest an altered HPA axis.
Edit to add: forum thread for this paper
Whole blood gene expression in adolescent CFS: altered B cell differentiation and survival, 2017, Nguyen et al

Although most elements appear permanently silenced in adult cells [96,97], environmental factors, including exogenous infections, may compromise their restriction [98-100]. Importantly, differential expression of HERVs in fibromyalgia and ME/CFS has been evidenced by several groups [101,102].

I'd like to know if this statement is true too.
101. Ovejero T, Sadones O, Sánchez-Fito T, Almenar-Pérez E, Espejo JA, Martín-Martínez E, et al. Activation of transposable elements in immune cells of fibromyalgia patients. Int J Mol Sci. 2020;21(4):1366. PubMed | CrossRef

102. Rodrigues LS, da Silva Nali LH, Leal CO, Sabino EC, Lacerda EM, Kingdon CC, et al. HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome. Auto Immun Highlights. 2019;10(1):1-5. PubMed | CrossRef


I'm left wondering what the point of this paper was.

 

[Andy]

I'm left wondering what the point of this paper was.

The paper ends with
"Conclusion
Is the immune dysregulation hypothesis proven?

After over 20 year of attempting to identify specific immune defects and infectious agents that cause ME/CFS, clear pathways are still not evident. However, a complex interaction between the immune system and viruses/retroviruses is now emerging and manifesting subtle changes in cytokines, NK cells and T cells which directly or via autoimmunity may be responsible for the plethora of symptoms seen in ME/CFS. Combined with immune and pathogen-induced mitochondrial dysfunction now being dissected by several research groups it is quite possible that it will gain real insight into the cause of this enigmatic and highly disabling illness."

so the point of the paper seems to be to show why they couldn't live up to the promise of the title?

 

[Hubris]

Treatment of established ME/CFS is therefore difficult and requires multi-specialty input addressing each of the areas affected by the illness.

A lot of people have been saying this, for decades, but no study has ever been done where they try, let's say an immune drug, an antiviral drug and a mitochondrial drug(or supplements) together and the patients get better. No evidence whatsoever for this statement.

 

[Hutan]

The unpredictable nature of seemingly unconnected and diverse symptoms that are poorly responsive to several allopathic and alternative therapies then contributes to an escalation of the illness with secondary dysfunction of multiple other systems.

Treatment of established ME/CFS is therefore difficult and requires multi-specialty input addressing each of the areas affected by the illness.

Yes, it's like they don't want to say 'there is no effective treatment'.

'poorly responsive to several allopathic and alternative therapies'
Allopathic medicine is

A system in which medical doctors and other healthcare professionals (such as nurses, pharmacists, and therapists) treat symptoms and diseases using drugs, radiation, or surgery. Also called biomedicine, conventional medicine, mainstream medicine, orthodox medicine, and Western medicine.

So, they are saying the symptoms are poorly responsive to several conventional drugs and alternative therapies. It's such an odd way to phrase it. It certainly doesn't rule out BPS therapies. It doesn't even rule out drugs and alternative therapies that aren't those 'several'.

 

[Sean]

Yes, it's like they don't want to say 'there is no effective treatment'.

Shades of Stone, and BrightCandle's comment on it.

 

[Hutan]

The reference for this is
10. Nguyen CB, Alsøe L, Lindvall JM, Sulheim D, Fagermoen E, Winger A, Kaarbø M,et al. Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. J Transl Med. 2017;15(1):1-21.PubMed | CrossRef
I'd like to have a look at that study as it's not obvious to me from the paragraph how, collectively, the findings suggest an altered HPA axis.
Edit to add: forum thread for this paper
Whole blood gene expression in adolescent CFS: altered B cell differentiation and survival, 2017, Nguyen et al

I checked out that reference, my commentary is on that linked thread.

It most definitely is not evidence for an altered HPA axis. Not even remotely. Unequivocably, not.

I won't say what I want to say about these authors. But if researchers don't take the time to actually read and think about the papers they cite, then it suggests that 'clear pathways' will still not be evident in another 20 years.

 

[Milo]

These may contribute to reactivation of previous acquired viruses/retroviruses accompanied by impaired endocrine regulation and mitochondrial energy generation.

Retroviruses, really? Please provide proof of this, other than XMRV of course

 

[SNT Gatchaman]

Expanding the paper's quote up-thread on HERVs:

A non-excluding possibility to explain ME/CFS symptoms and their relationship with immune dysregulation, is as result of aberrant activation of human endogenous retrovirus (HERVs). HERVs are dormant viral sequences incorporated in our genome through evolution which actually represent about 8% of our genome (~four times the size of protein-coding sequences)). Acquired through ancient exogenous infections they provide essential functions and the main source for human evolution.

Although most elements appear permanently silenced in adult cells, environmental factors, including exogenous infections, may compromise their restriction. Importantly, differential expression of HERVs in fibromyalgia and ME/CFS has been evidenced by several groups. Furthermore, HERV activation has been found in lymphocytes of COVID patients correlating with inflammatory markers and pneumonia ́s severity. Thus, the possibility that Long-COVID, a post-viral syndrome with symptoms that overlap those of ME/CFS, derives from the incapacity of some patients to re-silence HERVs seems to deserve interrogation. Symptomatically, HERV activation may translate into infection-like symptoms, such as pain, fatigue, immune and metabolic disturbances which are common in ME/CFS.

Their reference [98] to lymphocytes in COVID is Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients (2021). I don't think we have a thread on that but its abstract contains:

HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients.

The ME and fibromyalgia specific HERV references [101, 102] do have threads (though it doesn't appear we were very impressed with the ME paper, not least with "CFS/MS" which persists in the accepted paper):

• HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
• Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

 

[Tom Kindlon]

Free:
https://maplespub.com/article/what-...functional-immune-system-and-viral-infections

Review Article | Open Access2022|Volume 3|Issue 2|
https://doi.orG/10.37191/Mapsci-2582-6549-3(2)-033
What Causes ME/CFS: The Role of the Dysfunctional Immune System and Viral Infections
Amolak S Bansal1*, Aletta D Kraneveld2, Elisa Oltra3 and Simon Carding4

1Consultant in Immunology, Allergy and CFS/ME, Spire Bushey Hospital, Watford, UK

2Chair Interdisciplinary Translational Pharmacology, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht the Netherlands

3Department of Pathology, Faculty of Medicine and Health Sciences, Catholic University of Valencia, Valencia, Spain

4Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK and Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK

*Corresponding Author: Amolak S Bansal,Consultant in Immunology, Allergy and CFS/ME, Spire Bushey Hospital, Watford, UK.

ReceivedAug 12, 2022 RevisedAug 22, 2022 AcceptedAug 29, 2022 Published
Sep 16, 2022

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains an enigmatic highly disabling and complex long-term condition with a wide range of aetiologies and symptoms.

A viral onset is commonly mentioned by patients and several bodily systems are ultimately disturbed.

The parallel with long-covid is clear. However, immune dysregulation with impaired NK cell dysfunction and tendency to novel autoimmunity have been frequently reported.

These may contribute to reactivation of previous acquired viruses/retrovirusesaccompanied by impaired endocrine regulation and mitochondrial energy generation.

The unpredictable nature of seemingly unconnected and diverse symptoms that are poorly responsive to several allopathic and alternative therapies then contributes to an escalation of the illness with secondary dysfunction of multiple other systems.

Treatment of established ME/CFS is therefore difficult and requires multi-specialty input addressing each of the areas affected by the illness.

Keywords
Myalgicencephalomyelitis/chronic fatigue syndrome (ME/CFS), Immune system, Viruses, Retroviruses, Cytokines, NK cells, Mitochondria

From Mastodon:

https://disabled.social/@invest_in_me_research@mas.to

Invest in ME Research@invest_in_me_research@mas.to


@tomkindlon @mecfs
From our 10th annual International Biomedical Research into ME Colloquium (#BRMEC10). Agenda was created with help of EMERG (European ME Research Group) to test popular hypotheses that explain the aetiology of ME-including: immunogenetics and dysfunctional immune responses; abnormal autonomous nervous system and autoimmunity; mitochondrial metabolic dysfunction; and altered host-microbe (commensal and pathogen) interactions.
This was result of discussions from one hypothesis

https://mas.to/@invest_in_me_research/109514264314178437