NIH Funded Study to Identify ME/CFS Antibody Biomarkers..

[voner]

Interesting summary by Dr. Suzanne Vernon... 6 subtypes of ME/CFS .... Armin Alaedini, PhD of Columbia University ...

"Antibody biomarkers could be used to delineate a viral ME/CFS subtype from an autoimmune ME/CFS subtype from gastrointestinal ME/CFS subtype."

https://batemanhornecenter.org/identifyingantibodybiomarkers/

perhaps Suzanne would expand on this, perhaps here in this forum?

 

[roller]

from the OP:

Dr. Alaedini proposed a study to further characterize the intestinal immune response in ME/CFS and examine whether it could be associated with bacteria moving across the gut and instigating inflammation.
He submitted his application in January 2015 for the NIH ME/CFS funding opportunity

is one year for approval normal?

 

[Justin30]

Good news...I like it...keep it coming....

 

[Simon]

Looks interesting to me, not least because it's focusing on a sub-group - those with gut problems - which should help finding a biomarker a lot easier. They have preliminary data, and a $200k grant should give a decent sample size as they have access to well-diagnosed patients (often the most expensive part) via the Bateman Horne Center.
BHC Collaborates on NIH Funded Study to Identify ME/CFS Antibody Biomarkers

Although the lead researcher, Alaedini Armin is from Columbia Uni, he's from Columbia University Health Sciences, ot Ian Lipkin's Center for INfection and Immunity

Project Information - NIH RePORTER -

DESCRIPTION (provided by applicant):
A major barrier to a better understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been the heterogeneity within the condition and the lack of biomarkers to characterize disease phenotypes and analyze treatment outcome. While the etiology and pathogenesis of ME/CFS are poorly understood, there is evidence that immune system abnormalities are associated with symptoms in a substantial number of affected individuals.

In addition, many ME/CFS patients complain of gastrointestinal (GI) symptoms of unknown etiology. However, immune responses to dietary and microbial antigens as underlying causes of the reported GI symptoms or as contributors to systemic inflammation have not been explored in controlled studies. Our preliminary data from a study of well-characterized patients and controls demonstrate that individuals with ME/CFS exhibit significantly elevated antibody reactivity to gluten, which correlates with the severity of GI symptoms.

Moreover, the results show that the observed immune response to gluten in ME/CFS is fundamentally distinct from that in celiac disease, being independent of the action of transglutaminase 2 enzyme and HLA-DQ2/DQ8 molecules. Additional data within this application indicate that increased antibody reactivity to gluten can be associated with microbial translocation in individuals without celiac disease.

We hypothesize that the molecular targets of the antibody response to gluten in ME/CFS are unique, further characterization of which may identify novel biomarkers of the condition, and that this immune response is associated with microbial translocation and systemic inflammation in a subset of ME/CFS patients.

To analyze the molecular targets of the identified immune reactivity and assess its implications for ME/CFS, we propose two specific aims.

• In Aim 1, we will map the antigenic specificity of the immune response to gluten in ME/CFS through mass spectrometry-assisted proteome analysis and epitope mapping.
  
• In Aim 2, we will assess the relationship between the immune response to gluten and specific markers of microbial translocation and systemic inflammation in ME/CFS.

The information that is expected to emerge if the aims of the proposed project are achieved would
1) offer biomarkers that may be useful in identifying subsets of patients or individuals at risk of developing ME/CFS,
2) support the examination of specific treatment strategies targeted at the identified subset of patients, and
3) yield experimental support for closer examination of the role of intestinal barrier defects and aberrant mucosal immune response in the pathophysiology of ME/CFS.

This grant proposal is in line with the program announcement's (PAR-12-033) request for applications that "examine the etiology, diagnosis, pathophysiology, and treatment of chronic fatigue syndrome", such as the identification "of environmental, including dietary, precipitants" and the development of "novel and objective biological markers for the diagnosis of ME/CFS".

 

[duncan]

Alaedini is a name familiar to the Lyme community, particularly PTLDS. I am not overly fond of some of the folks he has historically published with.

Interesting how there is an increasing overlap between Lyme research and ME/CFS research.

ETA: I believe he has done similar gluten-type studies as to how markers might be demonstrated in psychosis and schizophrenia.

 

[Alexi]

Dr Rostami in the UK has special interest in non coeliac gluten sensitivity

 

[RustyJ]

I find this study interesting because of the gluten intolerance angle in particular. I suspect some ME patients are actually undiagnosed celiacs. Many patients have resorted to going gluten-free with only minimal impact on their symptoms. However, such patients may need to remove other foods know to be gluten cross reactive from their diets.

Although I have been gluten free for years without any real progress, I recently started a diet free of gluten cross reactive foods (in addition to gluten) and had significant improvement to my gastro issues, to the extent that I have been able to reduce my medications by 80% within a matter of weeks.

My personal history may be of interest to those with similar symptoms. I have gastro intestinal issues along with cognitive and PEM and OI and meet ICC. I was diagnosed non-celiac by biopsy and gluten intolerant by blood test.

I was able to moderate the gastrointestinal bloating and reflux by taking proton pump inhibitors and H2 blockers as well as going gluten-free. However my GI issues were still significant. I have been gluten free for about 10 years. I noticed no reduction in any other symptoms.

My ME symptoms in general have slowly worsened to the extent that I am out of bed for at most 2 hrs a day and even then I am unsteady, weak and have some vertigo.

By chance, I recently came across an article about Dermatitis herpetiformis, a blistery rash associated with CD, particularly during teen age years. I recall that I did have this issue for about five years, mainly on my hands and feet during my teenage years. Doctors said they believed it was something caused by stress (meaning they didn't know what it was).

Suspecting that I may have CD, I also chased up material on diagnosing celiac disease and now believe that testing for CD can be very unreliable, due to many factors, including false negatives, new understandings of the disease pathways, whether or not the sufferer has begun a gluten-free diet, and methodology.

Furthermore, there is also a body of research that links neurological issues to gluten intolerance, with some research suggesting that there is more than one pathway to celiac symptoms.

I also came across several articles and some research that focussed on celiacs not improving after going gluten-free, but who later did improve after removing so-called gluten cross reactive foods from their diets as well as gluten.

Previously, I had tried many times to reduce the medications for my GI problems, without success. Yet within two weeks of removing cross-reactive foods from my diet I am now almost medication-free. I have less bloating and no reflux at all.

I have no relief from my other symptoms, but this may take considerable time.

Note, the diet is savage. No coffee, milk, eggs, potato, grains, nuts. Death may be preferable. However some of the articles suggested you may be able to add these back in after some months.

 

[sdmcvicar]

from the OP:



is one year for approval normal?

Usually that means that you got a near-approvable score but need to modify the research plan slightly and then re-submit. If there's no notice of approval in the next couple of months, then a different proposal would need to be submitted in order to get funding.

 

[JaimeS]

This certainly seems interesting. As someone with ME symptoms and suspected gluten sensitivity, I'd love to hear more about this!

-J

 

[Tuha]

This is interesting - I have also GI problems. I had some food tests and the gluten stuffs and kazein were the most problematic in my case.
A doctor did a test also for opioid peptides and they were also elevated but they dont know yet what does it mean. He told me that similar problems we can often see in autism. He said that the kids with autism often gets better after gluten free and kazein free diet.

 

[JaimeS]

This is interesting - I have also GI problems. I had some food tests and the gluten stuffs and kazein were the most problematic in my case.
A doctor did a test also for opioid peptides and they were also elevated but they dont know yet what does it mean. He told me that similar problems we can often see in autism. He said that the kids with autism often gets better after gluten free and kazein free diet.

Gluten has opioid-like chemicals, as does dairy.

-J

 

[cigana]

Our preliminary data from a study of well-characterized patients and controls demonstrate that individuals with ME/CFS exhibit significantly elevated antibody reactivity to gluten, which correlates with the severity of GI symptoms.

Moreover, the results show that the observed immune response to gluten in ME/CFS is fundamentally distinct from that in celiac disease, being independent of the action of transglutaminase 2 enzyme and HLA-DQ2/DQ8 molecules. Additional data within this application indicate that increased antibody reactivity to gluten can be associated with microbial translocation in individuals without celiac disease.

We hypothesize that the molecular targets of the antibody response to gluten in ME/CFS are unique, further characterization of which may identify novel biomarkers of the condition, and that this immune response is associated with microbial translocation and systemic inflammation in a subset of ME/CFS patients.

This is interesting, does anyone know if we've discussed these findings before on PR?

I wonder if it relates to Lipkin's upcoming paper on the gut...

 

[cigana]

As far as I understand it they are suggesting microbial translocation is the issue rather than gluten - it's just that the gluten can be used as a means of studying the break down of the gut barrier.

 

[Tuha]

Gluten has opioid-like chemicals, as does dairy.

-J

it´s possible. I am not good in medical stuffs. Everything what I understood that they didnt know to much about it yet. They just proposed in authistic kids to keep gluten and kazein free diet and often they have positive results with it

 

[panckage]

As far as I understand it they are suggesting microbial translocation is the issue rather than gluten - it's just that the gluten can be used as a means of studying the break down of the gut barrier.

This leads perfectly into what I wanted to ask about. Do people with gluten sensitivity and CFS find they onset at about the same time?

According to what you wrote above it probably shouldn't be. Is that correct?

 

[cigana]

This leads perfectly into what I wanted to ask about. Do people with gluten sensitivity and CFS find they onset at about the same time?

According to what you wrote above it probably shouldn't be. Is that correct?

As far as I can see Gluten intolerance can happen at any age, so I think you're correct.

It would mean that people with both CFS and gluten sensitivity might develop them at about the same time (assuming the gluten sensitivity is due to the breakdown of the gut barrier).

 

[panckage]

It would mean that people with both CFS and gluten sensitivity might develop them at about the same time

OK interesting in my personal case gluten sensitivity started a couple years before the onset of CFS. I am a far from typical case as I am intolerant to many many things though (gluten, soy, all spices I have tried, cocoa, onions, broccoli, Bok choi, etc)

 

[JaimeS]

This leads perfectly into what I wanted to ask about. Do people with gluten sensitivity and CFS find they onset at about the same time?

According to what you wrote above it probably shouldn't be. Is that correct?

I definitely noticed my sensitivity to gluten got worse at onset. I was always able to tolerate dairy just fine before, but now it's the one food that if I touch, I stop being able to breathe! It's a dramatic change.

-J

 

[RustyJ]

Just a follow up on my previous post in this thread about gluten cross reactivity. Here is a good link to an easy to read article which itself has links to research.

My progress since that post continues to show improvement. Over the period of four to five weeks on the autoimmune gluten free diet (which excludes cross reactive foods as well as gluten), I am now off all digestion-related medication and have less stomach related symptoms than I had when fully medicated.

For the first time in 20 years I have no stomach bloating and minimal reflux. My headaches have gone. I was taking 18-20 panadol a week and my headaches were increasing. Other symptoms such as OI, PEM etc remain.

Some other symptoms eg cognitive difficulties, weakness may have improved but it is too early to tell, as these symptoms can vary over time somewhat.

 

[JaimeS]

Just a follow up on my previous post in this thread about gluten cross reactivity. Here is a good link to an easy to read article which itself has links to research.

Great article, and somewhat relieving to someone who's started avoiding all grains of all kinds because she reacts to so many. I might try adding some of those non-reactors back into my diet...

-J