USA: Center for Solutions for ME/CFS - news and updates from Columbia University's NIH funded center

[V.R.T.]

Lipkins fundraiser has not done very well so far since the large donation that started it off, and I am concerned it is because the wording implies that they do not have any plans for clinical trials in the next five years. Under the section about what they planned to do with the next five years of NIH funding.

I'm not sure what their actual plans are but that would run counter to his recent statements.

Perhaps some clarity on their clincal trial plans would make people more willing to donate? However I understand that they may currently be sensitive and subject to experiments that aren't yet complete.

 

[forestglip]

Health Rising: 'The Best of Times, The Worst of Times: Ian Lipkin Talks on ME/CFS'

“I am so, I am so encouraged. I am so eager. And anybody watching this podcast, (and there’s one person in particular, Ron) don’t give up hope. I really think we’re almost there. You know, it just, you know, I, I get these notes sometimes from people who say, you know, I want to donate my, my body for your research.

And I say, please don’t… just hang in there”. He rued the young, formerly healthy people he’d known who’d committed suicide, and said, “We’re almost there. It does seem like so many things are tying together.”

Includes an interview with Ian Lipkin:

 

[V.R.T.]

Health Rising: 'The Best of Times, The Worst of Times: Ian Lipkin Talks on ME/CFS'



Includes an interview with Ian Lipkin:

So does Lipkin have a history of these statements like Klimas does? Or is this out of character and therefore a little more believable?

Of course he is trying to get his funding turned back on, so who knows.

But it does seem we are seeing more and more of these statements...

 

[V.R.T.]

Health Rising: 'The Best of Times, The Worst of Times: Ian Lipkin Talks on ME/CFS'



Includes an interview with Ian Lipkin:

Lipkin mentions a 1999 finding of antibody titers to 'all sorts of things that are not even found in nature'

@Jonathan Edwards isn't there something in your hypothesis about antibody response to 'junk' antigens?

This bit...

We suggest that in ME/CFS, antibodies with relatively low affinity for antigens available on an ongoing basis contribute to disease indirectly by being taken up, together with such antigens, by high-affinity FcγRI on gamma interferon-primed macrophages and thereby facilitating presentation of antigen to T cells[58]. Both CD4 and CD8 T cells might thus be activated, the latter via cross-presentation of antigen on MHC Class I. These antibodies may have high affinity for previously encountered microbes and may have undergone affinity maturation in some past immune response but are relevant because they bind with relatively low affinity to what might be called ‘everyday junk’ antigens that may include antigens derived from gut flora, low-level persistent viruses such as Herpes, partially degraded self proteins with post-translational modifications, or possibly normal host signal pathway proteins, such as heat shock proteins and proteasome components, upregulated during immune responses.

What do you make of the claims Lipkin makes that are quoted in the message above and in the healthrising article? Can you say if it's related to any of the stuff coming down the pipeline that you have spoken about on here?

 

[Jonathan Edwards]

I have heard of this comment from Lipkin before but I never saw any data for it and I have never heard Jo Cambridge refer to it and she has been working on B cell sin MECFS for ten years.

Health Rising has never been a very useful source of information!

 

[V.R.T.]

I have heard of this comment from Lipkin before but I never saw any data for it and I have never heard Jo Cambridge refer to it and she has been working on B cell sin MECFS for ten years.

Health Rising has never been a very useful source of information!

He claims its in a paragraph near the end of a paper, not sure which one. So i guess no data are provided.

Yes I'm aware r.e. health rising, I was more wondering in terms of Lipkins claims about his work than any editorial spin that might have been put on it.

 

[wigglethemouse]

I have heard of this comment from Lipkin before but I never saw any data for it and I have never heard Jo Cambridge refer to it and she has been working on B cell sin MECFS for ten years.

In case it helps, I posted about it on the hypothesis thread (link) and on the 2020 thread for Lipkins B cell IGHV3-23/30 paper (link)

 

[Jonathan Edwards]

The only comment in the results for the Borna paper was that there were antibodies to galactosidase.
I am not sure that one can extrapolate from that to a claim for polyclonal B cell activation. But it would be consistent with what we have called 'looser control' of antibody specificity.

 

[wigglethemouse]

I am not sure that one can extrapolate from that to a claim for polyclonal B cell activation. But it would be consistent with what we have called 'looser control' of antibody specificity.

The video transcript in the post I linked describes antibodies to things not encountered in nature. That falls within your description I think.

but i was impressed at that point as were my colleagues by the observation that people with mecfs in the swedish cohort had very high levels of antibodies to a wide range of things some of them that you don't even encounter in nature so at the tail end of our paper we said we find no evidence that this particular virus is important in mecfs but we do find evidence of abnormalities in the immune system suggesting that this is a biologically based disorder

 

[Jonathan Edwards]

The video transcript in the post I linked describes antibodies to things not encountered in nature. That falls within your description I think.

Yes, I am not sure that is a very useful description since we all have 'antibodies to things not found in nature'. At least some of those will also be antibodies to things found in nature that may be hard to identify ( previous infections maybe). Others may be 'natural antibodies' especially if IgM. Antibodies to plastic are of course ubiquitous, which is why you have to 'block' ELISA plates with casein or something similar, but that is a very non-specific electrostatic effect so maybe a red herring.

If Lipkin had thought it important then presumably he would have followed it up. It would be fairly easy to replicate. Maureen Hanson's group have recently provided some perhaps more helpful data, which do show some broad differences. Jo Cambridge also has some data that hopefully will be published fairly soon. There do seem to be shifts but it isn't that easy to interpret them. The old idea of 'polyclonal B cell activation' may have been a bit simplistic. It may usefully apply to Sjogrens patients with hypergammaglobulinaemia but otherwise things are a bit more complicated.

 

[V.R.T.]

Maureen Hanson's group have recently provided some perhaps more helpful data, which do show some broad differences

Is this in a published paper or forthcoming?

 

[Hoopoe]

I remember that my serum protein electrophoresis curves were outside of the norm early in the illness, at two different time points.

Albumin levels were low and one of peaks was outside the norm.

Also, I was treated for low iron levels, without apparent cause. Several lymph nodes were also enlarged which caused some discomfort. None of this was abnormal enough to be considered concerning or lead to a diagnosis but maybe it was some subtle ways the illness showed itself.

 

[Jonathan Edwards]

Is this in a published paper or forthcoming?

It was published fairly recently. We have discussed it. They didn't find any increase in well recognised autoantibodies. There were some differences between sexes, but I forget quite what.

 

[V.R.T.]

It was published fairly recently. We have discussed it. They didn't find any increase in well recognised autoantibodies. There were some differences between sexes, but I forget quite what.

Ah - I assume you mean this one:

Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome

Significance
Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a serious disabling chronic illness that lacks FDA-approved therapies.

Comprehensive transcriptomic, epigenomic, and flow cytometric profiles of primary CD8+ T cell subsets implicate T cell exhaustion in pathophysiology. We show that T cells in ME cases are epigenetically predisposed toward terminal exhaustion and that exhaustion markers are upregulated following exercise challenge. Using single-cell genomics, we provide important information about the role of CD8+ T cell exhaustion development and progression.

Our findings are consistent with the hypothesis that chronic viral infection is a factor in ME; by dissecting the molecular basis of T cell dysfunction in ME, we offer potential avenues for treatment.

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a severe, debilitating disease, with substantial evidence pointing to immune dysregulation as a key contributor to pathophysiology.

To characterize the gene regulatory state underlying T cell dysregulation in ME, we performed multiomic analysis across T cell subsets by integrating single-cell RNA-seq, RNA-seq, and ATAC-seq and further analyzed CD8+ T cell subpopulations following symptom provocation. Specific subsets of CD8+ T cells, as well as certain innate T cells, displayed the most pronounced dysregulation in ME. We observed upregulation of key transcription factors associated with T cell exhaustion in CD8+ T cell effector memory subsets, as well as an altered chromatin landscape and metabolic reprogramming consistent with an exhausted immune cell state. To validate these observations, we analyzed expression of exhaustion markers using flow cytometry, detecting a higher frequency of exhaustion-associated factors.

Together, these data identify T cell exhaustion as a component of ME, a finding which may provide a basis for future therapies, such as checkpoint blockade, metabolic interventions, or drugs that target chronic viral infections.


https://www.pnas.org/doi/epub/10.1073/pnas.2415119121

 

[Jonathan Edwards]

This one:

Int J Mol Sci 2025 Mar 20;26(6):2799.
doi: 10.3390/ijms26062799.

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques​

Arnaud Germain , Jillian R Jaycox, Christopher J Emig, Aaron M Ring, Maureen R Hanson

 

[V.R.T.]

This one:

Int J Mol Sci 2025 Mar 20;26(6):2799.
doi: 10.3390/ijms26062799.

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques​

Arnaud Germain , Jillian R Jaycox, Christopher J Emig, Aaron M Ring, Maureen R Hanson

How bizarre - I found the T cell one, thought it probably wasnt that, looked further, found the autoantibody one you linked and then accidentally linked the T Cell one instead! I suppose I had both tabs open. Damn brain fog!