New Genetic Links to MS Also Play Roles in Other Autoimmune Diseases

[Annikki]

http://www.sciencedaily.com/releases/2011/08/110810132848.htm

This is an adjunct to this article:

Multiple Sclerosis Research Doubles Number of Genes Associated With the Disease, Increasing the Number to Over 50

ScienceDaily (Aug. 10, 2011) Dr. John Rioux, researcher at the Montreal Heart Institute, Associate Professor of Medicine at the Universit de Montral and original co-founder of the International Multiple Sclerosis Genetics Consortium is one of the scientists who have identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of a very debilitating neurological disease. Many of the genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.

http://www.sciencedaily.com/releases/2011/08/110810141255.htm

 

[Annikki]

Here's one genetic commonality to MS and another autoimmune disease: p53
http://www.ncbi.nlm.nih.gov/pubmed/16178012

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1939966/

 

[Enid]

Thanks Annikki - very interesting research findings.

 

[kurt]

We need a study like this for ME/CFS. Why has nobody conducted a full genomic profile for us? That should be the starting point for any serious research into any major disease now, given the increasing affordability of that type of data. In fact, I would like to know why the major ME/CFS research organizations are not working together like this, or promoting the idea that a full genomic profile study is essential to move research forward.

 

[Annikki]

We need a study like this for ME/CFS. Why has nobody conducted a full genomic profile for us? That should be the starting point for any serious research into any major disease now, given the increasing affordability of that type of data. In fact, I would like to know why the major ME/CFS research organizations are not working together like this, or promoting the idea that a full genomic profile study is essential to move research forward.

I fully agree- genetic profiles would go a long way in research. Be glad these diseases are related. Learning from other research could show ME/CFS researchers where to start looking for genetic answers in ME/CFS.

Asking why we have just successfully decoded the dog genome but don't have good genetic research for this debilitating disease is a good question- but a sad one.

I'm reading through the MS findings. They are worth looking at. Autoimmune diseases have more in common with each other than most people think.

I wonder if any genetic researchers could be enticed to take up an ME/CFS project.

 

[Mark]

You're right of course, Kurt, this is a critical area to focus on. What is the CFIDS Association funding in this area? The only gene study I know of is Dr Kerr's and it seems that has fallen through the cracks like everything else. But one good study that found the same or similar genetic patterns to the MS one would be a massive breakthrough. With the prices of genetic testing going down all the time, surely it will become economic to research us properly some time soon?

One thing I read about this study in the press was one of the researchers saying that (very probably) the inflammation comes first and that exposes the immune vulnerabilities. The question then, of course, is what's causing the inflammation? For persistent (chronic) conditions, viruses that the immune system can't clear would seem the obvious candidate. But other transient environmental triggers could perhaps trigger the cascade of immune dysfunction.

Anyway, it looks increasingly likely to me that MS and all the other 'auto'-immune conditions are going to turn out to have very similar explanations...and with MS similar in so many ways to ME - similar enough that many people flip between the two diagnoses - any MS research has to be of interest to us. And it does seem to me that the findings of genetic links make it very hard to argue that psychological factors are of any great relevance in causing these illnesses...the argument that the immune abnormalities could be the downstream consequence of self-destructive patterns of thought and behaviour is rather harder to advance when those abnormalities are genetic...

This new research looks very promising too - novel sensory pathway modulating Th17 pro-inflammatory cells:
http://forums.phoenixrising.me/showthread.php?13202

I think all this research is going to come together soon; progress seems inexorable, and False Illness Beliefs (FIBs) don't seem to be part of this picture...

 

[Annikki]

I agree with you Mark. Surely something is amiss on a genetic level with a few of these diseases. I did a simple search about p53 and MS for instance. I chose p53 because this is one gene I'm already familiar with. p53 is a gene involved in one other autoimmune disease I'm aware of and many cancers. p53 controls cell apoptosis which is cell death which is instigated by the body itself. In cancer, p53 is defective- it fails to instruct defective cancer cells to self-destruct. Normally it plays a role in protecting the body from cancer but it does become defective. Here's a study showing the role between p53 and MS:

Defective ATM-p53-mediated apoptotic pathway in multiple sclerosis.
Deng X, Ljunggren-Rose A, Maas K, Sriram S.
Source

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. xinqing.deng@vanderbilt.edu
Abstract

Defective elimination of autoreactive cells is thought to play a role in the development of autoimmune diseases including multiple sclerosis (MS). We examined the activation of the ATM-CHK2-p53 pathway in MS patients after subjecting their peripheral blood mononuclear cells to gamma-irradiation. We found that peripheral blood mononuclear cells from a subset of MS patients show resistance to cell death induced by irradiation. This defect is due to impaired constitutive expression and activation of ATM (ataxia telangiectasia mutated), resulting in impaired stabilization of p53. We predict that these fundamental defects likely alter the regulation of the immune population of cells in MS and may contribute to the development or progression of the disease.

Link: http://www.ncbi.nlm.nih.gov/pubmed/16178012

Another autoimmune disease called interstitial cystitis, p53 has been found to be at fault. For an unknown reason, bladder epithelial cells get killed off from by p53 even though these cells aren't cancerous in IC patients: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1939966/

It is important to know viruses can cause bad behavior from p53. Epstein Barr Virus is found to alter activity of gene p53:
http://www.fhcrc.org/science/education/courses/cancer_course/basic/molecular/accumulation.html
Even EBV is associated with p53 malfunction:
"rognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer,"
http://www.ncbi.nlm.nih.gov/pubmed/17020977
Studies have been done which have blocked p53 in Murine retrovirus caused Leukemia (note that p53 plays a role in over 50% of cancers):http://www.ncbi.nlm.nih.gov/pubmed/8642629
http://www.ncbi.nlm.nih.gov/pubmed/8642629
There are are other viruses like HPV (human papilloma viruses), adenoviruses and simian virus 40 which play a role in modulating p53 behavior.
http://www.nature.com/nrc/journal/v9/n10/box/nrc2718_BX1.html

My personal thought is that p53 is one gene playing a role in all the different autoimmune diseases. As for the why and how, I can't tell you. P53 is likely playing a role through cell destruction in instigating cell damage in immune cells and other cells in the body.

My bet is that the studies on MS will reveal where to look in ME/CFS, fibro and more. No other autoimmune diseases are privy to genetic research right now. The finding of p53 involvement in interstitial cystitis is circumstantial.

Let's hope for the best from these studies.

 

[Enid]

More and more interesting - thanks Annikki.!

 

[Annikki]

You're welcome!

 

[Annikki]

I was working on finding which genes have been implicated by that study on Multiple Sclerosis when I found an article which summarizes the study. The main thing researchers found, says the article, about MS is:

Described in the Aug. 11, 2011 issue of the journal Nature, the study compares genetic material from tens of thousands of individuals in the United States and Europe, including 10,000 people with multiple sclerosis.

It identified 50 distinct genetic loci, or regions of DNA sequences, that contribute to multiple sclerosis. These loci do not necessarily indicate specific genes that cause the disease but rather locations on the genome where there may be genes and genetic variations that influence someones risk of developing the disease.

http://www.ucsf.edu/news/2011/08/10...tiple-sclerosis-reveals-dna-hot-spots-disease

The article identifies three separate components involved in the development of MS:

Exposure to environmental factors like smoking, UV radiation, and toxins

Post-genomic, epigenetic and regulatory events; these include gene arrangements, messenger RNA splicing or editing, retroviral sequences, methylation and microRNAs (this fits well with the other thread about the new anti-inflammatory drug being developed, which works by mopping up the DNA and RNA fragments which can trigger an inflammatory reaction by the body).

Genomic allelic variants These include: single nucleotide polymorphisms, insertion/deletion polymorphisms, disease modifier genes, disease susceptibility genes and copy number variations.

I find this very interesting. It seems retroviruses play a role in the findings as well as environmental factors.


As for a specific gene which is modified in MS, I found this older study about a gene involved in autoimmune diseases:
http://www.nature.com/news/2010/100616/full/news.2010.300.html
This seems to hold true when comparing a unique chemical found only in patients with another autoimmune disease, which is composed in part of sailic acid.
http://www.pnas.org/content/101/32/11803.abstract