Biomarker for ME/CFS found?!?

[Seanko]

Griffith University in Australia are claiming to have found a biomarker for ME/CFS

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.

Report on ME Action about Biomarker story below

Australian scientists announce they have made a breakthrough in Chronic Fatigue Syndrome testing, now looking for partners to bring a diagnostic test to market.

An ABC radio interview with Australian scientists at Queensland’s Griffith University reveals they have identified new markers on white blood cells which can be used to screen patients. Patient Lyn Wilson, Professor Don Staines and Professor Sonya Marshall Gradisnik are interviewed.

• Listen to the interview or read the transcript

Several published and as-yet-unpublished studies contributed to this stage, see the abstract for the study, ‘A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis’.

The study, conducted on 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. In CFS/ME patients, a marker called CD127 was significantly decreased on all subsets of CD8+ T cells. PSGL-1 was significantly reduced.

News reports are hailing the finding as a possible biomarker:

DAVID MARK: Australian scientists say they could soon produce a diagnosis for Chronic Fatigue Syndrome that could be as simple as having a blood test.

The scientists have identified new markers on white blood cells which can be used to screen patients who present with symptoms characteristic of chronic fatigue.

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.

– report by Courtney Wilson on ABC’s PM program

From Griffith University’s media release:

The research team from the National Centre for Neuroimmunology and Emerging Diseases (NCNED), Menzies Health Institute Queensland, has identified new markers that can be used to screen patients and is now looking to partner with diagnostic companies to bring a test to market. The screening test is expected to benefit all those with symptoms of the condition.

“Over the last four years, with support from the Queensland Government and philanthropic donors, we have identified unique markers in CFS patients,” says Professor Marshall-Gradisnik.

“This screening test may be expected to become a laboratory standard to provide more certain, and cost-efficient, diagnosis for CFS. Currently patients may be undergoing a range of tests to diagnose for CFS which incurs a significant cost to the health care system."

“CFS, also known as myalgic encephalomyelitis (ME), affects up to 400,000 Australians, many of whom are housebound or bedbound. Patients are isolated and further stigmatised by disbelief of their condition.

“This illness has traditionally been difficult to diagnose, meaning that people can go for months without getting the care and attention they require. We are confident that the new screening test currently in development will provide efficient and increasingly accurate screening for people with CFS. This test may also be used to monitor and track the progression of their illness,” says Professor Staines.

 

[Seanko]

Source paper in Journal of Immunology Research A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Ekua W. Brenu,1 Simon Broadley,2 Thao Nguyen,1,3 Samantha Johnston,1,3Sandra Ramos,1 Don Staines,1 and Sonya Marshall-Gradisnik1,3

1The National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Gold Coast, Australia
2School of Medicine, Griffith University, Gold Coast, Australia
3School of Medical Science, Griffith University, Gold Coast, Australia

Abstract

Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naïve, central memory (CM), effector memory CD45RA− (EM), and effector memory CD45RA+ (EMRA) cells.

Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls.

Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings.

 

[Seanko]

Story covered on Australian Radio

| MP3 DOWNLOAD
DAVID MARK: Australian scientists say they could soon produce a diagnosis for Chronic Fatigue Syndrome that could be as simple as having a blood test.

The scientists have identified new markers on white blood cells which can be used to screen patients who present with symptoms characteristic of chronic fatigue.

The team behind the breakthrough at Griffith University in Queensland say understanding the pathology behind Chronic Fatigue Syndrome will help to legitimise the disease.

Courtney Wilson reports.

COURTNEY WILSON: At 39, Lyn Wilson's life was turned upside down when she was diagnosed with Chronic Fatigue Syndrome.

But it wasn't just the diagnosis that rocked her.

It took 16 months from the onset of her first symptoms before Ms. Wilson could actually put a name to what was wrong.

LYN WILSON: It's a complete and utter exhaustion that, no matter how much you rest, you don't recover from.

COURTNEY WILSON: How difficult was that window of time between when you had symptoms and when you were diagnosed?

LYN WILSON: It was terrible. At one stage lost the feeling in my legs for 24 hours and then came back with pins and needles and I was assured that I would get a diagnosis.

Went to see a neurologist and he turned around and said, "You're just overweight, unfit and should go join an aerobics class."

So, you know, you did not get any sympathy along the way.

COURTNEY WILSON: With a broad spectrum of symptoms which vary from patient to patient, Chronic Fatigue Syndrome is notoriously difficult to diagnose.

That's why the breakthrough by scientists studying the disease at Griffith University in Queensland is so significant.

Professor Don Staines says it's been years in the making.

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.

COURTNEY WILSON: The discovery could mean that soon, a simple blood test is all it takes to confirm a diagnosis of Chronic Fatigue Syndrome.

Professor Staines again.

DON STAINES: We're looking at changes in very specific parts of gene that then translate to certain receptors or proteins in the body that have key roles in metabolism, neuronal function, cardiovascular function and so on, so it's probably not surprising that it's taken this long to work it out.

COURTNEY WILSON: It's estimated some 400 000 Australians suffer Chronic Fatigue Syndrome, which leaves some people bedbound.

Symptoms vary from mental confusion and concentration loss to unexplained pains, gastrointestinal disturbance and even cardiovascular problems.

Professor Sonya Marshall Gradisnik says the research team is now looking to partner with diagnostic companies to develop the test to bring to market.

She says when that happens, it will have a huge impact for people who suffer from chronic fatigue syndrome.

SONYA MARSHALL GRADISNIK: I think it would expedite their diagnosis. It also would expedite recognition of illness, legitimise the illness and propel area of intervention.

COURTNEY WILSON: Lyn Wilson says from her experience, the impact of a quick, accurate diagnosis can't be underestimated.

SONYA MARSHALL GRADISNIK: It was just such a relief, and the diagnostic specialist kept saying, you know, "It's a terrible illness". But I was so relieved, I just couldn't wipe the smile off my face, I was just so pleased to finally know what it was.

COURTNEY WILSON: Professor Don Staines says it could still take several years before a blood test for chronic fatigue syndrome becomes available in Australia.

But, he says, when it happens, it will change peoples' thinking around the condition.

DON STAINES: Everyone will understand that this is a very disabling illness. It has very concrete pathology and hence gives people the reassurance that this is a very genuine illness, an extremely incapacitating illness and one that GPs and the general community will understand better.

LYN WILSON: For it to be a legitimate illness and be recognised by all doctors and be able to be as simple as having a blood test would be just phenomenal.

DAVID MARK: Chronic Fatigue Syndrome sufferer Lyn Wilson, ending that reporting by Courtney Wilson.

 

[Strike me lucky]

I received a recent email about a new study and looking for participants. It appears they are going to study spinal fluid and blood? A few proviso's, no recent infections and no recent steroid use. Bugger those two count me out after shingles and prednisolone use. Partial copy of email. Title says 'Brain scan cfs study'.


Thankyou for expressing interest in our upcoming studies investigating Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Our research depends on the generosity of those suffering from this illness of all severities as well as healthy controls. May I please start by asking you to confirm your location as this will influence any appointment I can book for you to participate in our studies.


May I please ask you to have a look over the criteria below and reply with regards to which points you may or may nor meet. Please be aware that there is some flexibility regarding some points (e.g. medications) so please feel free to reply with additional information where relevant. Participants are required to meet these criteria in order to ensure the results from our studies are the most accurate.


·Females or males between the ages of 18 to 80 years old

·If a healthy control: Experiences no problems with severe fatigue (ie. Fatigue is relieved after bed rest)

·If affected by fatigue: Experienced severe fatigue for at least 6 months (ie. Fatigue is not relieved after bed rest). No other health problem that would explain the fatigue.

·Not housebound and can travel to the site of the study.

·Non-smoker or has not smoked for the last 2 years

·Medications including natural therapies and any anti-inflammation medication should be discontinued 2 weeks before blood donation. Some medications such as paracetamol and oral contraceptives are permissible.

·Body Mass Index (BMI) less than 30

·No current/previous diagnosis of a chronic illness eg. autoimmune, neurological, cancer, cardiovascular, Type 1 diabetes, primary psychiatric, major infectious disease (eg. tuberculosis, HIV)

·Not currently suffering from a cold, flu or other illness at the time of donation or in the previous 7 days

·Must not be pregnant or breast feeding

·No recent history of major surgery

·Willing to donate 85ml of blood and complete the online/hard copy Questionnaire. You will be asked to complete the full survey as well as a shorter one closer to your appointment. You are welcome to complete this questionnaire now if you wish.
https://prodsurvey.rcs.griffith.edu.au/prodls190/index.php?sid=66993&lang=en

 

[Strike me lucky]

I didnt mention but this study is being done at Griffith Univerity on the Gold Coast, Australia .

 

[Seanko]

@Strike me lucky Has there been much coverage in the Australian media of the story?

 

[Cort]

Griffith University in Australia are claiming to have found a biomarker for ME/CFS
Report on ME Action about Biomarker story below

Australian scientists announce they have made a breakthrough in Chronic Fatigue Syndrome testing, now looking for partners to bring a diagnostic test to market.

An ABC radio interview with Australian scientists at Queensland’s Griffith University reveals they have identified new markers on white blood cells which can be used to screen patients. Patient Lyn Wilson, Professor Don Staines and Professor Sonya Marshall Gradisnik are interviewed.

Listen to the interview or read the transcript,

Several published and as-yet-unpublished studies contributed to this stage, see the abstract for the study, ‘A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis’.
The study, conducted on 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. In CFS/ME patients, a marker called CD127 was significantly decreased on all subsets of CD8+ T cells. PSGL-1 was significantly reduced.
News reports are hailing the finding as a possible biomarker:

DAVID MARK: Australian scientists say they could soon produce a diagnosis for Chronic Fatigue Syndrome that could be as simple as having a blood test.

The scientists have identified new markers on white blood cells which can be used to screen patients who present with symptoms characteristic of chronic fatigue.

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.

– report by Courtney Wilson on ABC’s PM program​

From Griffith University’s media release:

The research team from the National Centre for Neuroimmunology and Emerging Diseases (NCNED), Menzies Health Institute Queensland, has identified new markers that can be used to screen patients and is now looking to partner with diagnostic companies to bring a test to market. The screening test is expected to benefit all those with symptoms of the condition.

“Over the last four years, with support from the Queensland Government and philanthropic donors, we have identified unique markers in CFS patients,” says Professor Marshall-Gradisnik.

“This screening test may be expected to become a laboratory standard to provide more certain, and cost-efficient, diagnosis for CFS. Currently patients may be undergoing a range of tests to diagnose for CFS which incurs a significant cost to the health care system.

“CFS, also known as myalgic encephalomyelitis (ME), affects up to 400,000 Australians, many of whom are housebound or bedbound. Patients are isolated and further stigmatised by disbelief of their condition.

“This illness has traditionally been difficult to diagnose, meaning that people can go for months without getting the care and attention they require. We are confident that the new screening test currently in development will provide efficient and increasingly accurate screening for people with CFS. This test may also be used to monitor and track the progression of their illness,” says Professor Staines.

Wow - I don't think they've made this kind of claim before. They must be quite confident in their results. I see that they've been working on this for years so they have more data than has been reported. Time to start digging! This could be big news

 

[Cort]

CD127 - important immune receptor on T-cells. Problems with the protein have been associated with an immunodeficiency disease as well as MS and RA. They found the same immune deficits in MS and ME/CFS (!)...That's good news!

What is the biomarker, though, that differentiates ME/CFS from MS?

Then Staine talks about a gene - not a protein. Is a gene polymorphism the biomarker or the receptor on the cell?
_________________________________

https://en.wikipedia.org/wiki/Interleukin-7_receptor

Interleukin-7 receptor has been shown to play a critical role in the development of immune cells called lymphocytes - specifically in a process known as V(D)J recombination[citation needed]. This protein is also found to control the accessibility of a region of the genome that contains the T-cell receptor gamma gene, by STAT5 and histone acetylation[citation needed]. Knockout studies in mice suggest that blocking apoptosis is an essential function of this protein during differentiation and activation of T lymphocytes. Functional defects in this protein may be associated with the pathogenesis of severe combined immunodeficiency (SCID).[4]
Diseases

Several diseases are associated with Interleukin-7 receptor including T-cell acute lymphoblastic leukaemia,[5] multiple sclerosis,[6] rheumatoid arthritis and juvenile idiopathic arthritis.[7]

 

[Cort]

I received a recent email about a new study and looking for participants. It appears they are going to study spinal fluid and blood? A few proviso's, no recent infections and no recent steroid use. Bugger those two count me out after shingles and prednisolone use. Partial copy of email. Title says 'Brain scan cfs study'.


Thankyou for expressing interest in our upcoming studies investigating Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Our research depends on the generosity of those suffering from this illness of all severities as well as healthy controls. May I please start by asking you to confirm your location as this will influence any appointment I can book for you to participate in our studies.


May I please ask you to have a look over the criteria below and reply with regards to which points you may or may nor meet. Please be aware that there is some flexibility regarding some points (e.g. medications) so please feel free to reply with additional information where relevant. Participants are required to meet these criteria in order to ensure the results from our studies are the most accurate.


·Females or males between the ages of 18 to 80 years old

·If a healthy control: Experiences no problems with severe fatigue (ie. Fatigue is relieved after bed rest)

·If affected by fatigue: Experienced severe fatigue for at least 6 months (ie. Fatigue is not relieved after bed rest). No other health problem that would explain the fatigue.

·Not housebound and can travel to the site of the study.

·Non-smoker or has not smoked for the last 2 years

·Medications including natural therapies and any anti-inflammation medication should be discontinued 2 weeks before blood donation. Some medications such as paracetamol and oral contraceptives are permissible.

·Body Mass Index (BMI) less than 30

·No current/previous diagnosis of a chronic illness eg. autoimmune, neurological, cancer, cardiovascular, Type 1 diabetes, primary psychiatric, major infectious disease (eg. tuberculosis, HIV)

·Not currently suffering from a cold, flu or other illness at the time of donation or in the previous 7 days

·Must not be pregnant or breast feeding

·No recent history of major surgery

·Willing to donate 85ml of blood and complete the online/hard copy Questionnaire. You will be asked to complete the full survey as well as a shorter one closer to your appointment. You are welcome to complete this questionnaire now if you wish.
https://prodsurvey.rcs.griffith.edu.au/prodls190/index.php?sid=66993&lang=en

Spinal fluid and blood -they're looking for the marker or some markers in both - that's good - they wouldn't do that unless they had an idea that something was going to be found in both - and if they find the same thing in both compartments - that's really strong evidence. If they can do it that would be a big finding...

 

[Seanko]

@Cort My knowledge of the immune system has come on quite a bit in the last year but it's not enough to decipher the detail.
Could you contact some of your expert acquaintances for an impartial take?

 

[voner]

here is a recent publication by them on gene polymorphisms in ME/CFS ......

http://www.la-press.com/redirect_fi...-Potential-Melastatin-M3-Ion.pdf&fileType=pdf

 

[Veet]

·Medications including natural therapies and any anti-inflammation medication should be discontinued 2 weeks before blood donation.

leaves me out.

 

[IrisRV]

What is the biomarker, though, that differentiates ME/CFS from MS?

Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls.

[my bolding]
At a quick glance, it looks like the PSGL-1 finding was unique to PWME as well.

This is stupendous news, not just because we might have biomarkers, but because this may point to the pathogenesis of ME. Immune abnormalities, imagine that.

 

[Strike me lucky]

@Strike me lucky Has there been much coverage in the Australian media of the story?

To be honest, not really. The cfs community know about this research but the average guy in the street would still say yuppie flu.

They are well funded by a trust fund designated for cfs, donated by a cfs patient who inherited alot of money from her father. Also the state government here donate the majority.

The aim of their work was to find a diagnostic marker and initially were doing specific nk function testing between nk dim and nk bright cells. Not sure if it was specific enough to cfs. But they have done more studies on cytokines and t cells etc as well.

As far as i know they arent looking ito treatments yet just diagnostic test.

 

[Strike me lucky]

leaves me out.

Im thinking of emailing them.of specifics of the last month or so and see if i can go in the trial??

 

[IrisRV]

Im thinking of emailing them.of specifics of the last month or so and see if i can go in the trial??

Could it be that they don't need to collect samples immediately? Some of these things take months to get going.

I'm always disappointed in the 'better than housebound' requirement. I understand that they can't afford to come to patients, but they could also be missing so much. OTOH, they're getting some interesting results with their limited cohort, so perhaps the limited sample is good enough to start with.

I love the way Griffith is looking at a variety of immune factors, not just one or two.

So... how does this fit in with the autoimmune theory?

 

[Cort]

@Cort My knowledge of the immune system has come on quite a bit in the last year but it's not enough to decipher the detail.
Could you contact some of your expert acquaintances for an impartial take?

I don't know that mine is either....I will try and find someone...

 

[Cort]

To be honest, not really. The cfs community know about this research but the average guy in the street would still say yuppie flu.

They are well funded by a trust fund designated for cfs, donated by a cfs patient who inherited alot of money from her father. Also the state government here donate the majority.

The aim of their work was to find a diagnostic marker and initially were doing specific nk function testing between nk dim and nk bright cells. Not sure if it was specific enough to cfs. But they have done more studies on cytokines and t cells etc as well.

As far as i know they arent looking ito treatments yet just diagnostic test.

They've also found the same dysfunction T-cells that has been found in NK cells - they're not good at killing bad cells.

 

[Strike me lucky]

Could it be that they don't need to collect samples immediately? Some of these things take months to get going.

I'm always disappointed in the 'better than housebound' requirement. I understand that they can't afford to come to patients, but they could also be missing so much. OTOH, they're getting some interesting results with their limited cohort, so perhaps the limited sample is good enough to start with.

I love the way Griffith is looking at a variety of immune factors, not just one or two.

So... how does this fit in with the autoimmune theory?

They did do studies on severe cfsers that were bed bound etc. So they dont leave them out all the time which is good.

Probably right that by the time they are ready to test people it will be abit later.

 

[Strike me lucky]

They've also found the same dysfunction T-cells that has been found in NK cells - they're not good at killing bad cells.

Yes the original study i was in over an 18month period did nk function and cd8 t cell function study and other markers. But we only got our nk function and basic blood work result. No individual results for cd8 t cells but as a group they said cd8 function was low.

My gp also ran lymphocytic subset tests at the time which just give numbers. My nk cd56 were normal , nk cd3 high, cd4 and cd8 number also high. Maybe trying to over compensate for low function or maybe some type of immune exhaustion and t cells are being produced to rapidly and are immature??? Just my speculation.

Heres a copy of one of my test results of one test 2011. I think on this test the ranges are a combo of cfs and healthy controls in the study.
Original normal nk activity range was 14 to 35.
Nk dim cells 60 to 88
Nk bright cells 5 to 15.