NVCBR researchers close in on a diagnostic test for ME/CFS patients

Kati

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News from the Nevada Center for biomedical research:

NVCBR researchers close in on a diagnostic test for ME/CFS patients

They explain where their most recent research is taking them, from this recently published paper featured on this thread

NVCBR researchers close in on a diagnostic test for ME/CFS patients
Physicians lack effective tools to aid in the diagnosis and treatment of those who are impacted by ME/CFS, a complex and often disabling disease. That could change now that scientists at Nevada Center for Biomedical Research (NVCBR) have taken the first step in developing a clinical assay for diagnosing ME/CFS patients through the creation of an antibody immune signature.

The work was conducted in collaboration with Drs. Stephen Johnston and Phillip Stafford, at Arizona State University’s Biodesign Institute, Innovations in Medicine, and Drs. Karen Schlauch and Richard Tillet, from the University of Nevada, Reno, as well as other researchers from around the world.

The group’s findings recently appeared in the prestigious journal Molecular Neurobiology http://bit.ly/2h55uXC.

The immune system produces proteins called antibodies that bind to the surface of pathogens, such as viruses and bacteria, to neutralize the pathogens. Occasionally, this system becomes dysregulated and produces antibodies to our own tissue, resulting in autoimmunity. Utilizing a microchip comprised of thousands of small random protein sequences (referred to as random peptides), researchers at NVCBR, in collaboration with the scientists at ASU’s Biodesign Institute, screened blood sera from ME/CFS cases and healthy controls, from two geographic distinct cohorts, and identified a diagnostic pattern of antibody/peptide binding that identifies ME/CFS patients with high specificity and sensitivity.

“The purpose of screening sera with a random peptide array is to identify things that our body sees as foreign such as the molecules that make up pathogens or the proteins of our own tissue, in the context of autoimmunity,” explained Dr. Vincent Lombardi, NVCBR Research Director. “Now that we have identified a group of random peptides that differentially bind with the antibodies of ME/CFS patients, our next challenge is to figure out what antigens these random peptides represent in the real world. Much can be learned about the causes of this disease once the antigens are accurately identified.”


Read the full article by clicking the title.
 

drob31

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This would suggest it's autoimmune. Interesting about the high reactivity of antibodies to HIV, and also to certain gut bacteria.
 

alex3619

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I wonder how compatible this test model is with the one proposed by NCNED and involving intracellular calcium and calcium channels? They do not appear to be compatible, though its clear that subsets might exist under both models that could be measuring the same problem with two different techniques.

Its up to both groups to adequately validate their model and make the full data set available to the scientific community.
 
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I wonder how compatible this test model is with the one proposed by NCNED and involving intracellular calcium and calcium channels? They do not appear to be compatible, though its clear that subsets might exist under both models that could be measuring the same problem with two different techniques.

Its up to both groups to adequately validate their model and make the full data set available to the scientific community.
I'm going with some vague notion that the antibodies are highly tuned to attack and knock out, erm, calcium responsible, erm, things (highly scientific terminology there, but I hope you get the idea).

Or else otherwise, the calcium problem happens first, which then leads to something, perhaps the unused calcium itself, being identified as foreign, that otherwise wouldn't be.

Will be VERY eye opening when they identify the real world targets if these antibodies. Heh, imagine if it really was calcium itself. Got milk?
 

user9876

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Having a quick flick through their paper I'm not convinced that their results are solid. If I read it correctly (which I may not have done) they used a boot strap method to pull data from their set of samples and train a classifier but the results they quote are over their full data set. Really they should have a separate set to look at for results otherwise there is a danger that they are picking up on details of the data they have rather than having a good model. But their results are very good which suggests they may have something.
 

RogerBlack

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Having a quick flick through their paper I'm not convinced that their results are solid. If I read it correctly (which I may not have done) they used a boot strap method to pull data from their set of samples and train a classifier but the results they quote are over their full data set. Really they should have a separate set to look at for results otherwise there is a danger that they are picking up on details of the data they have rather than having a good model. But their results are very good which suggests they may have something.
The study was of 21 patients and 21 controls.
If you start going down to 10 patients and 10 controls for your test and learning sets, the statistical power of the test goes way down.

The next step is a larger cohort, to see if it's real - not a rollout globally.
 

ScottTriGuy

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This would suggest it's autoimmune. Interesting about the high reactivity of antibodies to HIV, and also to certain gut bacteria.
From the paper:

"...identified a diagnostic pattern of antibody/peptide binding that identifies ME...When adjusted for protein size, the six most significant viral proteins with sequence homology to our random peptides were the gp120 protein of HIV (six hits); followed by the polyprotein of GB virus Ccpz (three hits)..."


Does this mean that the gp120 protein of HIV may especially provoke the immune system to produce antibodies?

Which are producing ME symptoms because they are erroneously attacking our bodies and not (just) the pathogen / HIV?

I ask for clarification for 2 reasons:

1) I am living with HIV for 18 years (but only with ME since Aug 2012), and

2) also because there is a lot of funding for HIV research that may:

A) have already uncovered data relevant to ME, or

B) be available for this unexplored area of HIV and autoimmunity...which may uncover data relevant to ME

Who is the researcher that gets GWI funding but also collects ME data? That sort of idea.
 

ash0787

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interesting alternative to the stanford approach, difficult to get a feel for how reliable this is going to be though, not a simple experiment at all
 

natasa778

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I wonder how compatible this test model is with the one proposed by NCNED and involving intracellular calcium and calcium channels? They do not appear to be compatible, though its clear that subsets might exist under both models that could be measuring the same problem with two different techniques.

Its up to both groups to adequately validate their model and make the full data set available to the scientific community.
"...identified a diagnostic pattern of antibody/peptide binding that identifies ME...When adjusted for protein size, the six most significant viral proteins with sequence homology to our random peptides were the gp120 protein of HIV (six hits); followed by the polyprotein of GB virus Ccpz (three hits)..."


gp120 protein binds to/affects calcium channels and dysregulates intracellular calcium, so that could be one thing linking both their findings.


http://www.pnas.org/content/97/9/4832.full.pdf
http://www.jneurosci.org/content/31/47/17074
http://www.sciencedirect.com/science/article/pii/S0014579310005715
https://www.ncbi.nlm.nih.gov/labs/articles/2326646/

etc you get the idea.

Purinergic/ATP signalling is also involved.
 

Hutan

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"...identified a diagnostic pattern of antibody/peptide binding that identifies ME...When adjusted for protein size, the six most significant viral proteins with sequence homology to our random peptides were the gp120 protein of HIV (six hits); followed by the polyprotein of GB virus Ccpz (three hits)..."
Googling GB virus Ccpz

http://ir.uiowa.edu/cgi/viewcontent.cgi?article=3095&context=etd

GB virus C (GBV-C) is a nonpathogenic lymphotropic virus that replicates in B and T lymphocytes.

Infection with GBV-C is documented worldwide and is common: between 1% and 5% of healthy blood donors are viremic at the time of donation. Antibodies to GBV-C proteins are not usually detected during viremia, and antibodies to the GBV-C envelope glycoprotein E2 develop following the clearance of viremia.

Although GBV-C viremia may persist for decades, viremia usually clears within 2 years following infection in the majority of individuals infected by blood transfusion. A chimpanzee variant of GBV-C, designated GBV-Ccpz, is found in captive and noncaptive chimpanzees and its prevalence and natural history are uncharacterized.

HIV-infected individuals who are co-infected with GBV-C survive longer than those without GBV-C. GBV-C infection of PBMCs inhibits the replication of HIV isolates and one of the mechanisms for this is the downregulation of HIV coreceptors and secretion of the coreceptor ligands. Additional mechanisms of HIV inhibition by GBV-C are examined in this dissertation.
 

alex3619

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gp120 protein binds to/affects calcium channels and dysregulates intracellular calcium, so that could be one thing linking both their findings.
There are lots of possibilities. However one of the issues, discussed in relation to this kind of research elsewhere, is we do not know what is really being bound by the antibody. These are linear sequences, not three dimensional conformations. I am aware that many receptor types might be bound, and lead to either gain or loss of function, but its far too early to be sure what is being bound.

That does not mean we cannot consider these to be useful clues for future research.

I much prefer the opposite approach, provide intact target proteins and see what antibodies bind to them from patient blood. Of course you have to have some idea about what proteins to isolate in order to test this way.

We will know more when they can isolate a group of target proteins and focus on whole protein interaction.

This is really a different facet of big data. They create a lot of data points. They identify likely candidates. They still have to validate specific interactions. Its like a big data pilot study. There is a long way to go. The risk of both false positives AND false negatives is high.

If this research does lead to a diagnostic test I think it will be more likely due to an amalgamation of data points, and there may not be much to link to specific disease processes. At least not without a very different style of experiment.