Biomarker for ME/CFS found?!?

weyland

Well-Known Member
So far I've only done some reading on CD127 (going to check out PSGL-1 next) but I'm not seeing how it would have any specificity as a test for ME. The same thing is found in untreated HIV patients, an increase in CD8+CD127- T cells. Upon antiviral treatment, they see CD127 expression increase.

Among other things, it appears that lack of CD127 expression on T cells is a sign of T cell activation, as you would expect would happen in a chronic infection or even noninfectious inflammatory diseases:

Recently, much attention has been attributed to another mechanism causing CD127 downregulation, namely, T-cell activation. Downregulation of CD127 by T-cell-activating factors has been also demonstrated in a number of animal and in vitro models [14]. Correspondingly, we and many other investigators reported decreased levels of CD127 expression on CD4+ and CD8+ T-cells in AIDS [15, 16]. Downregulation of CD127 on entire CD4+ T-cell pool (not only infected CD4+ T-cells) was demonstrated to reflect the status of chronic immune activation characteristic for lentiviral infection [17]. Decreased CD127 levels in HIV-infected individuals are strongly related to increased rate of disease progression, increased T-cell death resulting in CD4+ T-cell loss, and impairment of protective functional immunity [18, 19]. Similarly, we found significantly decreased CD127 on CD4+ T-cells in patients with noninfectious chronic inflammatory diseases characterized by T-cell activation, namely, perennial allergy and asthma [20]. Similarly, alterations of CD127 expression were reported in rheumatoid arthritis patients [21]. Moreover, experimental blockade of CD127 in arthritis mice resulted in significant clinical improvement [22].
Source

Perhaps there is something more specific about the combined finding of low CD127 and low PSGL-1? That would surprise me though.
 

IrisRV

Well-Known Member
Perhaps there is something more specific about the combined finding of low CD127 and low PSGL-1? That would surprise me though.
There must be something. This group of brilliant immunology researchers is not so stupid as to claim as a biomarker something that is so obviously non-specific. Either there's something more specific about the deficit or they are considering a combination of abnormalities to be diagnostic.

I don't see why the combined finding of low CD127 and low PSGL-1 would be surprising.

Hopefully we'll get more information soon.
 

weyland

Well-Known Member
Interesting (and good) that plasma IL-7 level doesn't appear to have much effect on CD127 (aka IL-7 receptor) expression, because a previous study found low IL-7 levels in ME patients.

...no correlation was found between plasma levels of IL-7 and either the percentage (Fig. 1D) or the absolute count (data not shown) of CD8+CD127− memory T cells. These results suggest that the prevailing plasma levels of IL-7, which are inversely correlated with CD4+ T cell counts in HIV-infected patients (29,30), do not determine the levels of IL-7R expression on CD8+ T cells. Because IL-7 has the potential to down-modulate CD127 expression both in vitro and in vivo (4, 31, 32, 33, 34), we sequentially measured CD127 expression on CD8+ T cells after ex vivo treatment with either rIL-7 or the mitogen PHA. As shown in Fig. 1E, we found that a transient down-modulation of CD127 follows treatment with rIL-7, whereas a more persistent loss of CD127 was observed when CD8+ T cells were treated with PHA. Taken together with the observation that the expansion of CD8+CD127− T cells correlates with the levels of immune activation but not with plasma levels of IL-7 (Fig. 1D), this result suggests that chronic antigenic stimulation may be more important than the plasma level of IL-7 in determining the unusual abundance of CD8+CD127− T cells seen in HIV-infected individuals.
Source
 

Strike me lucky

Well-Known Member
Even just combining several biomarkers like nk and cd8 function with some type of cytokine test along with Canadian consensus criteria. If individually they arent isolated just to cfsers, the combination i think would be a good starting point.

Once we have a more accurate way of testing cfs then they might find drugs are more effective when studied as they are now studied in the same group of patients not a mish mash of different patients which can occur using the basic criterias used on there own now. It will make other cfs research more accurate hopefully.

One example is that dr peterson has better success rates with ampligen then other drs which they say is because he carefully selects the patients he thinks are best suited. I have read that he thinks those with low nk function seem to get better results, so uses this as apart of his criteria for using ampligen??

There could be similar markers for those who may be rituximab responders or to other treatments. I think currently dishing out treatments just using the current criterias is a stab in the dark mostly.
 

IrisRV

Well-Known Member
Even just combining several biomarkers like nk and cd8 function with some type of cytokine test along with Canadian consensus criteria. If individually they arent isolated just to cfsers, the combination i think would be a good starting point.
I agree. Griffith, however, seems to be saying that they have a biomarker or biomarkers to identify ME/CFS from blood tests.
DON STAINES: We have found for the first time, specific markers, which can now be used in the form of a blood test to screen people who may present with symptoms of Chronic Fatigue Syndrome or myalgic encephalomyelitis to their GP.
As Cort asked above, could the biomarker be a gene polymorphism rather than just the receptor deficit?

Obviously, we don't have all the information yet. I'm eager to hear more.
 

weyland

Well-Known Member
So, similar to CD127 expression, it looks like PSGL-1 expression is also downregulated by immune cell activation:
In summary, the overall conclusion from the current data is that leukocyte activation results in decreased surface expression of PSGL-1 and decreased leukocyte adhesion to P-selectin under both static and dynamic conditions. The decrease in PSGL-1 surface-expression occurs along with the appearance of PSGL-1 in the supernatants. It is unclear at this time whether PSGL-1 release is the result of a novel divalent cation-dependent sheddase or some other mechanism. Finally, though much remains to be determined about the in vivo regulation of PSGL-1 expression, these findings indicate an entirely novel means by which leukocyte-leukocyte, leukocyte-platelet, and leukocyte-endothelial interactions, and thus many facets of the inflammatory response, may be regulated.
Source
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
There must be something. This group of brilliant immunology researchers is not so stupid as to claim as a biomarker something that is so obviously non-specific. Either there's something more specific about the deficit or they are considering a combination of abnormalities to be diagnostic.

I don't see why the combined finding of low CD127 and low PSGL-1 would be surprising.

Hopefully we'll get more information soon.
I'm going to ask them...
 

Gijs

Active Member
I was wondering how these immune markers are related to Lipkins study in patiënts who are 3 years or less sick. I think a single biomarker for CFS will never be found in a heterogene disease. Their findings don't mean anything at this point. So a breakthrough in this context is very misleading. I don't hope this is going to be the next XMRV scenario.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
I was wondering how these immune markers are related to Lipkins study in patiënts who are 3 years or less sick. I think a single biomarker for CFS will never be found in a heterogene disease. Their findings don't mean anything at this point. So a breakthrough in this context is very misleading. I don't hope this is going to be the next XMRV scenario.
Such optimism :bored: :)

I think there's a lot to learn about this finding. I'm going to give it a shot. I'll let you know.

I agree though that a single biomarker would be surprising...
 

Seanko

Well-Known Member
@Strike me lucky as you've taken part in NCNED studies at Griffith University, would you be able to broker an interview by @Cort ?
Cort could email the questions people have raised in this thread to Professor Marshall-Gradisnik.

The NCNED will be looking for publicity as it is seeking for market a test internationality & Cort would be the ideal person to ask the questions. :)
 

IrisRV

Well-Known Member
@Cort, I'd be interesting in knowing whether there is a length-of-illness variation in these immune markers, as in the Hornig-Lipkin finding.
 

Gijs

Active Member
Such optimism :bored: :)

I think there's a lot to learn about this finding. I'm going to give it a shot. I'll let you know.

I agree though that a single biomarker would be surprising...

As Always, i really like you optimism Cort :) What strikes me in investigation ME that there is a kind of allergy - autoimmune-like reaction to different things. Such as receptors and gluten etc...
 

Cindy T.

Member
If the researchers find someone to market the test for ME/CFS; does the FDA have to approve the test first? Do we have to go through a whole new litany of tests before they do? Just wondering how long it might be before there is a test available for the Americans, and is there room for hope? I am barely hanging on here, and will probably apply for disability before too long. The CFS is progressing. Having a test accepted by the powers that be (including SSI) would really help.
 

Seanko

Well-Known Member
For those that want to tackle CD8+ T (cytotoxic) cells, the British Society for Immunology has a guide (use it wisely)

Guide to CD8+ T cells

CD8+ (cytotoxic) T cells, like CD4+ Helper T cells, are generated in the thymus and express the T-cell receptor. However, rather than the CD4 molecule, cytotoxic T cells express a dimeric co-receptor, CD8, usually composed of one CD8α and one CD8β chain. CD8+ T cells recognise peptides presented by MHC Class I molecules, found on all nucleated cells. The CD8 heterodimer binds to a conserved portion (the α3 region) of MHC Class I during T cell/antigen presenting cell interactions (see Figure 1).

CD8+ T cells (often called cytotoxic T lymphocytes, or CTLs) are very important for immune defence against intracellular pathogens, including viruses and bacteria, and for tumour surveillance. When a CD8+ T cell recognises its antigen and becomes activated, it has three major mechanisms to kill infected or malignant cells. The first is secretion of cytokines, primarily TNF-α and IFN-γ, which have anti-tumour and anti-viral microbial effects.

[bimg=500|no-lightbox]http://bitesized.immunology.org/wp-content/uploads/2013/02/CD8-T-Cells-Figure-1.png[/bimg]

The second major function is the production and release of cytotoxic granules. These granules, also found in NK cells, contain two families of proteins, perforin, and granzymes. Perforin forms a pore in the membrane of the target cell, similar to the membrane attack complex of complement. This pore allows the granzymes also contained in the cytotoxic granules to enter the infected or malignant cell. Granzymes are serine proteases which cleave the proteins inside the cell, shutting down the production of viral proteins and ultimately resulting in apoptosis of the target cell.
The cytotoxic granules are released only in the direction of the target cell, aligned along the immune synapse, to avoid non-specific bystander damage to healthy surrounding tissue (see Figure 1). CD8+ T cells are able to release their granules, kill an infected cell, then move to a new target and kill again, often referred to as serial killing.

The third major function of CD8+ T cell destruction of infected cells is via Fas/FasL interactions. Activated CD8+ T cells express FasL on the cell surface, which binds to its receptor, Fas, on the surface of the target cell. This binding causes the Fas molecules on the surface of the target cell to trimerise, which pulls together signalling molecules. These signalling molecules result in the activation of the caspase cascade, which also results in apoptosis of the target cell. Because CD8+ T cells can express both molecules, Fas/FasL interactions are a mechanism by which CD8+ T cells can kill each other, called fratricide, to eliminate immune effector cells during the contraction phase at the end of an immune response.

In addition to their critical role in immune defense against viruses, intracellular bacteria, and tumours, CD8+ T cells can also contribute to an excessive immune response that leads to immunopathology, or immune-mediated damage.
 

knackers323

New Member
anyone know whats happened with this. keep hearing of new findings and breakthroughs and then it disappears and its never heard of again
 

Merida

Well-Known Member
@knackers323
Exactly. A lot of good thinkers and researchers here at healthrising, but still no clear answers. We are all struggling and hoping, exploring so many possibilities.
 

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