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Intriguing biomedical research outlined in CAA newsletter (Winter 2013)

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Exploratory research looking for biomarkers involving: genes, viruses, antibodies & auto-antibodies. There are a number of different avenues being explored.

Check out the ongoing exploratory biomedical research on pages 3-5 in the CAA's newsletter:
http://solvecfs.org/wp-content/uploads/2013/06/SolveCFS_Winter2013_FINALsmall.pdf

These researchers seem to be new to the field of ME/CFS. (I'm not familiar with them anyway.)
It seems to me that the calibre of these scientists will ensure that any promising results should lead to meaningful future research studies being carried out.


Pages 3-5; sections:

1. Discovering Biomarkers on Genes
Patrick McGowan PhD. (Assistant Professor in the Department of Biological Sciences at the University of Toronto at Scarborough.)

2. Virus Biomarkers
Eric L. Delwart PhD. (Professor of Laboratory Medicine at the University of California San Francisco and Blood Systems Research Institute.)

3. Antibodies as Biomarkers
Stephen J. Elledge PhD. (Howard Hughes Medical Institute in the Department of Genetics at Harvard Medical School.)

4. Autoantibody Biomarkers
Michael Cooperstock MD, MPH. (University of Missouri Health System.)
Madeleine Cunningham PhD. (University of Oklahoma)
David Kem MD (University of Oklahoma)
Armin Alaedini PhD (Columbia University)

5. Biomarker Validation
Michael Houghton PhD. (Canada Excellence Research Chair in Virology and Professor in the Department of Medical Microbiology & Immunology at the University of Alberta.)
(Houghton discovered the hepatitis C virus* and was awarded the 2000 Albert Lasker prize.)
[* I thought that it was Prof Harvey Alter who discovered Hep C, but it seems that they both had a part to play in a complex journey of discovery.]
 
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rosie26

Senior Member
Messages
2,446
Location
NZ
Fabulous Bob, thank you, I just went and deleted my above post just before you posted. It was frustrating me too much. Had to power out of my laptop 4 times as laptop was freezing. Will read tomorrow now as starting to get late here. xx
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
These are very interesting research questions, but I'm concerned about the criteria in the Solve CFS biobank. If there is no particular criteria (I have never been able to find that there is) or if the criteria is not specific enough, then it may be difficult to generalize or replicate the results, or to find significant results.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
These are very interesting research questions, but I'm concerned about the criteria in the Solve CFS biobank. If there is no particular criteria (I have never been able to find that there is) or if the criteria is not specific enough, then it may be difficult to generalize or replicate the results, or to find significant results.
This is the only info I've been able to find so far:
CAA said:
The current general enrollment criteria for the SolveCFS BioBank enables patients diagnosed by a physician using either the CCD or the 1994 Fukuda definition to participate, although all patients must have post-exertion malaise even though it is not required under the Fukuda definition. The Association also recommended that the American Psychiatric Association take note of the CCD in its written comments submitted on April 1, 2010 in response to feedback on the DSM-5 proposal.

The CFIDS Association consulted with Dr. Jason to ensure that the clinical questionnaires used for the SolveCFS BioBank will collect meaningful data that can be used to help overcome some of the definition issues that are huge challenges to the field. Having an established research network (as the Association does) and this biobank of blood/tissue samples AND extensive patient clinical information will be an enormous tool for the field and we hope the patient and scientific communities will support it.

http://www.cfids.org/about/faq.asp
 
Messages
16
Madeleine Cunningham PhD. (University of Oklahoma)


I am intrigued by Dr Cunningham's involvement here. She is a founder of Moleculera Labs at the University of Oklahoma, and is a leading expert on PANDAS. I have a child diagnosed with PANDAS over ten years ago. Another child started her journey toward an eventual ME/CFS diagnosis at almost the same time......
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
@Bob

Are you able to shed any light on the comment made in relation to the following:

4. Autoantibody Biomarkers
Michael Cooperstock MD, MPH. (University of Missouri Health System.)
Madeleine Cunningham PhD. (University of Oklahoma)
David Kem MD (University of Oklahoma)
Armin Alaedini PhD (Columbia University)

From the newsletter:

Despite the fact that samples for this study were selected from ME/CFS BioBank participants with brain fog and orthostatic intolerance, the rate of autoantibodies in ME/CFS patients compared to healthy controls was similar.

In other words, the types of autoantibodies detected by these investigators appear to be benign and not associated with ME/CFS. And even negative outcomes move us forward as we eliminate causes. There are many more autoantibodies to look at and their search continues.

Thanks :)
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
There was a Maes paper discussed on here a year or two back that showed we probably have massive levels of auto-antibodies, they just are not the ones that are normally looked for. Further we don't have just one type but many. It may also be the case that the antibody process is what is wrong, and that different patients have different sets of auto-antibodies. That will make conventional investigation, presuming the Maes research is accurate, very hard to do.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
OK. I shall go out on a limb here, Alex. I wouldn't trust anything published from Maes or Gerwyn for that matter let alone jointly. There. I said it.

Anyway, I'd like to read something from Cooperstock (as above). It might be that the comments relate to unpublished stuff I suppose, but it would be nice to know what they looked for and how. It could impact on the Rituximab stuff too I guess or at least be of use to those that are involved it trying to work out why Rituximab is seemingly working for some and not others.
 

user9876

Senior Member
Messages
4,556
I think there is something I don't get about the auto-antibodies. In reality aren't there just antibodies and some are labelled as auto-antibodies as they bind to or react with your own body rather (or as well as) than a pathogen. So how do you test for an auto-antibody as opposed to a normal antibody. Presumably there is a known set that cause or are associated with known diseases but I don't see how they would be relevant to ME since they suggest other disease. I guess you could test the antibodies against bits of tissue to see if they have an effect but that depends on tissue selection and finding a direct and easy to observe effect. As I understand it an antibody may react with a protein and the combination then may cause a problem elsewhere.

I also wonder if there could be an antibody that would bind to particular receptors in some people but not others depending on the exact nature of the receptors and peoples underlying genetics. Hence could it be possible to have normal antibodies that react in some people but not others?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Are you able to shed any light on the comment made in relation to the following:
Despite the fact that samples for this study were selected from ME/CFS BioBank participants with brain fog and orthostatic intolerance, the rate of autoantibodies in ME/CFS patients compared to healthy controls was similar.

In other words, the types of autoantibodies detected by these investigators appear to be benign and not associated with ME/CFS. And even negative outcomes move us forward as we eliminate causes. There are many more autoantibodies to look at and their search continues.
I don't have any further information re the specific details. In general terms, it seems that they were looking for some specific brain-related auto-antibodies (that they were perhaps familiar with from non-CFS research) perhaps with a specific model of disease in mind. And they couldn't find them (i.e. there were similar levels of autoantibodies in patients as in healthy controls.) But this only means that they didn't find the autoantibodies that they were looking for. It doesn't mean that autoantibodies don't exist in their samples.

I don't fully understand the following methodology that the article describes, so there may be more to their study than I am able to understand:
"...to test blood samples ... for autoantibodies against antigens in a human neural cell line, several specific human brain antigens and to mouse brain and dorsal root ganglion tissue."
 
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Bob

Senior Member
Messages
16,455
Location
England (south coast)
I think there is something I don't get about the auto-antibodies. In reality aren't there just antibodies and some are labelled as auto-antibodies as they bind to or react with your own body rather (or as well as) than a pathogen. So how do you test for an auto-antibody as opposed to a normal antibody. Presumably there is a known set that cause or are associated with known diseases but I don't see how they would be relevant to ME since they suggest other disease. I guess you could test the antibodies against bits of tissue to see if they have an effect but that depends on tissue selection and finding a direct and easy to observe effect. As I understand it an antibody may react with a protein and the combination then may cause a problem elsewhere.

I also wonder if there could be an antibody that would bind to particular receptors in some people but not others depending on the exact nature of the receptors and peoples underlying genetics. Hence could it be possible to have normal antibodies that react in some people but not others?
@Jonathan Edwards is the person to ask.
My guess is that they test for autoantibodies by searching for all present antibodies (any antibodies that they can detect), and if a patient cohort has a higher level of a specific antibody than a healthy control cohort, and no relevant virus (or similar antigen) is detectable in the patients, then you label it as an autoantibody.
And like you say, genes may perhaps play a role such that the same (auto)antibody reacts differently in different people, depending on small genetic differences.
I'm just guessing though. I haven't done much reading on autoimmunity.
 
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Snowdrop

Rebel without a biscuit
Messages
2,933
I've started to have a look at the first researcher, Patrick McGowan.
While the research may be fine I would be concerned about the conclusions drawn.
A lot of his research revolves around early childhood trauma, mental health and how that impacts our genetic makeup.
I have provided links to a few of the papers below:

http://www.sciencedirect.com/science/journal/01650270/174/1

http://www.sciencedirect.com/science/article/pii/S0969996109003817

http://www.nrcresearchpress.com/doi/abs/10.1139/bcb-2012-0070#.UrHg8yj0DoE

http://www.frontiersin.org/Journal/10.3389/fpsyt.2013.00110/abstract

A concept I found McGowan referred to in his research is 'biological embedding'. Here is a definition:

Biological embedding is the process by which experience gets under the skin and alters human biology and development. Systematic differences in experience in different social environments lead to different biological and developmental outcomes. These in turn influence health, well-being, learning, or behavior over the life course. Research at HELP contributes to our understanding of the process of biological embedding: how early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course.

from Human early learning partnership at UBC

Also, I couldn't link this directly so here's a copy and paste:
From: Journal of Neuroscience Methods Sept 2008

http://www.sciencedirect.com/science/journal/01650270/174/1


The effects of PH on DNA methylation state

Abstract

Assessment of methylation state of DNA extracted from brain is becoming one of the most investigated issues in the study of epigenetics and psychopathology. pH effects in brain are known to affect gene transcription, though pH effects on DNA methylation state are unknown. We demonstrate in vitro using an artificially methylated plasmid that DNA methylation state remains stable, even under extreme pH conditions. Next, using two different genomic regions from human DNA, we assess methylation state from both cortical and sub-cortical brain regions using subjects with varying pH levels. No correlation was found between DNA methylation state and pH. These results suggest that DNA methylation state is stable in post-mortem brain.

Article Outline

  1. 1. Introduction
  2. 2. Materials and methods
  1. 3. Results
  2. 4. Discussion

My bad if I repeated anything, I'm getting tired.