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OMF-funded research: T cells and molecular immunology

Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
Hi guys,

It’s #OMFScienceWednesday!

For the next few weeks, we will be describing the research projects that OMF is funding all over the world. The first project is about T cells and molecular immunology of ME/CFS, at the ME/CFS Collaborative Research Center at Stanford under the direction of Dr. Ron Davis. This project is a collaboration with Stanford professors Dr. Mark Davis, an expert in immunology, and Dr. Lars Steinmetz, an expert in genetics and gene expression.

We are hopeful that it will provide a new level of understanding into the immunological basis of ME/CFS.

Many studies have highlighted issues with the immune system in ME/CFS, ranging from altered cytokines to impaired NK cell function. Recently, Dr. Mark Davis’ team discovered evidence of clonal T cell expansion in ME/CFS patients – meaning that the killer T cells responsible for eliminating infected cells are making copies of themselves. Expansion happens when there is an active infection that the immune system is fighting, but it can also happen in autoimmunity, when the immune system mistakenly attacks the body’s own cells. Dr. Steinmetz’s team has developed new technologies to sequence single T cells and measure their gene expression. Understanding the behavior of these expanded T cells and what they are targeting will help us to better understand – and hopefully treat – ME/CFS. For example, it’s possible that some patients’ T cells are reacting to a microbial infection, and that some may have a truly autoimmune disease – which could in turn point to treatment via antimicrobials or immunomodulation.

To explore these possibilities, this project includes the following objectives, in a group of 25 ME/CFS patients this year:

Capturing and sequencing single T cells using these new technologies for identifying clonally expanded T cells and measuring their expression of thousands of genes, to understand their function in ME/CFS. The technologies were pioneered in tuberculosis patients, and the team is now hard at work optimizing them for ME/CFS patient samples.

Sequencing key immune-related genes: HLA and KIR. These genes – whose variants are associated with risk for infectious and autoimmune disease – are very difficult to sequence using traditional methods, so Dr. Ron Davis and his collaborators have developed better methods! Applying them here may help to interpret the other immunological data from this project.
Identifying the targets of expanded T cells. These may be infectious or autoimmune targets, and as described above, identifying them will reveal important insights into ME/CFS and its effects on the immune system of these patients.


Exciting stuff,


B
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
We are hopeful that it will provide a new level of understanding into the immunological basis of ME/CFS.

Many studies have highlighted issues with the immune system in ME/CFS, ranging from altered cytokines to impaired NK cell function. Recently, Dr. Mark Davis’ team discovered evidence of clonal T cell expansion in ME/CFS patients –

Exciting stuff,

Truly an outstanding direction for ME/CFS research to be taking!:thumbsup::thumbsup::thumbsup:

@Ben H thanks for posting and keeping us all updated!

"ScienceWednesdays" are great!
 

AdamS

Senior Member
Messages
339
Very exciting stuff, thanks for continuing to post OMF Science Wednesdays, they always give me a little mental boost for some reason!!

Also @Ben H i’m not sure if you’ve seen this article but it’s very recent and seems like quite a significant finding...may be worth sharing with Ron & Mark. Cheers
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Identifying the targets of expanded T cells. These may be infectious or autoimmune targets, and as described above, identifying them will reveal important insights into ME/CFS and its effects on the immune system of these patients.

Truly very exciting stuff! If they can identify the target(s) of expanded T cells, it could be a huge turning point in CFS research!!:thumbsup: Fingers crossed.;)

Jim
 

ebethc

Senior Member
Messages
1,901
@Ben H

Thanks for sharing this news.

Is there any synergy between the work in cancer immunotherapy and CFS? It seems like they're both trying to understand how the immune system misfires and how that can be redirected to defeat illness... Apparently, the cancer immunotherapy is most helpful in cancers that have a strong genetic component:


"The idea behind immunotherapy is to dismantle a molecular shield that some tumours use to avoid an attack by the body’s white blood cells.​

The immune system sees these tumours as foreign – they are fuelled by hundreds of genetic mutations, which drive their growth and are recognised by the body. But when white blood cells swarm in to attack the cancer cells, they bounce back, rebuffed.​

Immunotherapy drugs pierce that protective shield, allowing the immune system to recognise and demolish tumour cells. But the new drugs do not work against many common cancers."​


http://www.independent.co.uk/news/science/cured-unexpectedly-of-cancer-a8220826.html
 

AdamS

Senior Member
Messages
339
@Ben H
Is there any synergy between the work in cancer immunotherapy and CFS?

http://www.independent.co.uk/news/science/cured-unexpectedly-of-cancer-a8220826.html

Of course! Fluge & Mella’s work exemplifies that synergy. Btw interesting article thanks for posting. One of the drugs mentioned, nivolumab, seems to be useful in situations where T-cells are present but silent, ie, they have the brakes on and are unable to attack effectively, i’m not sure if that is the case in ME/CFS but i’m hopeful we will find out more soon which is very exciting.
 

ebethc

Senior Member
Messages
1,901
Of course! Fluge & Mella’s work exemplifies that synergy. Btw interesting article thanks for posting. One of the drugs mentioned, nivolumab, seems to be useful in situations where T-cells are present but silent, ie, they have the brakes on and are unable to attack effectively, i’m not sure if that is the case in ME/CFS but i’m hopeful we will find out more soon which is very exciting.

yes, the cancer immunotherapy work is interesting... fueled by $250m from the (Sean) Parker Foundation, a cancer research institute that brings together the best researchers from multiple universities so they can collaborate instead of compete and find a cure instead of just treating disease (b/c most $ comes from Pharma, who don't want to put themselves out of business w a cure!)...

https://www.sfgate.com/business/art...tute-to-lead-immunotherapy-trial-12210153.php

BTW - Sean Parker comes from a family w immune problems (some in his fam has hashimoto's, and he has life-threatening allergies.. I think peanuts put him into anaphylactic shock) so I wonder if he would donate to ME/CFS?? I bet someone in his family has CFS... I've always been surprised that no one in the CFS community has hit him up for a donation.. I bet he'd be amenable... Plus, there's traction now; it's not as "fringe" so it might be a good time to ask him or ask him again..

From 2015, this provides some background to his philanthropy and motivations:
https://www.buzzfeed.com/stephaniemlee/the-story-behind-sean-parkers-10-million-donation-to-autoimm

"Leading the new UCSF lab is Jeffrey Bluestone, an immunologist whose research has focused on the idea that therapies can reprogram the immune system to stop autoimmune diseases while maintaining its ability to fight infections. That’s in contrast to therapies that suppress abnormal immune functions, but can put patients at higher risk of developing infections. Some of Bluestone’s research has led to therapies that treat moderate to severe rheumatoid arthritis in adults and children, and that help keep your body from rejecting a transplanted kidney. He led research on an experimental drug designed to block the advance of type 1 diabetes that's now in clinical trials."​

Why can't this medical technology be used to destroy/break up LPS, infections and viruses (EBV, etc)? At a meta-level, are there some similarities?
 

AdamS

Senior Member
Messages
339
BTW - Sean Parker comes from a family w immune problems (some in his fam has hashimoto's, and he has life-threatening allergies.. I think peanuts put him into anaphylactic shock) so I wonder if he would donate to ME/CFS??

Wow, that’s the same Sean Parker who created Napster and was president at Facebook...I had no idea!