Epstein-Barr virus induced gene-2 upregulation identifies a particular subtype of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (2019) Kerr

[Sly Saint]

Provisionally accepted

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) is a chronic multisystem disease characterised by a variety of symptoms, and exhibits various features of an autoimmune-like disease.

Subtypes are well recognised but to date are difficult to identify objectively. The disease may be triggered by infection with a variety of micro-organisms, including Epstein-Barr virus (EBV). A subset of CFS/ME patients exhibit up regulation of EBV virus induced gene 2 (EBI2) mRNA in peripheral blood mononuclear cells (PBMC), and these patients appear to have a more severe disease phenotype and lower levels of EBNA1 IgG.

EBI2 is induced by EBV infection and has been found to be upregulated in a variety of autoimmune diseases. EBI2 is a critical gene in immunity and central nervous system function; it is a negative regulator of the innate immune response in monocytes. Its heterogeneous expression in CFS/ME could explain the variable occurrence of a variety of immune and neurological abnormalities which are encountered in patients with CFS/ME.

The EBI2 subtype occurred in 38-55% CFS/ME patients in our studies. Further work is required to confirm the role of EBV and of EBI2 and its oxysterol ligands in CFS/ME, and to identify the most practical means to identify patients of the EBI subtype. There are two EBI2 antagonists currently in development, and these may hold promise for the treatment of CFS/ME patients of the EBI subtype

https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full

full paper here:
http://sci-hub.tw/https://www.frontiersin.org/articles/10.3389/fped.2019.00059/full

I haven't read it all but not sure if I've posted it in the correct forum?:

"EBV reactivation is a model for psychological stress and triggering of CFS/ME"

 

[Andy]

"EBV reactivation is a model for psychological stress and triggering of CFS/ME"

That section talks about how "Psychological stress triggers release of glucocorticoids which activate EBV lytic infection through the upregulation of the immediate early BZLF1 gene expression" and explains how EBV reactivation has been seen in students and in military recruits - I think it's safely away from psychosocial research.

Just for interest, in checking his background, I found (or re-discovered - I, at least, can't remember it) this letter he wrote that was published by the BMJ in response to the article "Pressure grows on Lancet to review “flawed” PACE trial".

We can specifically treat several infective CFS/ME subtypes

Now that the biopsychosocial treatments, cognitive behavioural therapy (CBT) and graded exercise therapy (GET), are correctly recognised to be ineffective and even harmful (in the case of GET), it seems appropriate to reconsider what we can offer CFS/ME patients in terms of real benefit.

https://www.bmj.com/content/362/bmj.k3621/rr-11

 

[mariovitali]

From my presentation at EUROMENE (Sept. 2018) i propose the EBI2 as a target due to its association with Oxysterols. Slides 27 and 28 :





and

 

[Jonathan Edwards]

This is a review article titled to sound as if it is a data paper. As a review article it is poor. It is muddled and incorrect at almost every stage. It is impossible to work out what pathogenic mechanism is being proposed if any.

The mention of psychological stress is very strange. I don't think this is away from psychosocial research at all - certainly no further than Wessely or White who acknowledge the importance of viral initiation. The suggestion here is that psychological stress is of key importance in the causation of ME, yet it is also claimed that this indicates that ME is caused by viruses. The arguments seem to me incoherent. There is no evidence that I know of that psychological stress leads to reactivity of EBV infection.

We desperately need biomedical research but it has to be of a minimum standard. I don't think this reaches that minimum.