Nguyen et al/NCNED: Calcium mobilisation in NK cells from CFS/ME patients is associated with...

[hixxy]

This paper has been covered here:

Calcium mobilisation in natural killer cells from Chronic fatigue syndrome/Myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels

Mods can feel free to remove the thread.

 

[Never Give Up]

It looks like the same paper but the publication dates are 4 months apart, am I missing something?

@trishrhymes, they posted this simplified overview on their Facebook page today:

National Centre for Neuroimmunology and Emerging Diseases - NCNEDLike Page
3 hrs ·
NCNED describes calcium signalling disorder in CFS/ME

Our latest article (Nguyen et al., 2017) shows that certain ion channel receptors (called transient receptor potential ion channels or TRPs) responsible for calcium signalling in Natural Killer (NK) cells are defective, even when stimulated with their natural ligand.
We have used NK cells as a model to illustrate this pathology in all cells.

These current results indicate this ion channel is not functioning correctly and unable to modulate calcium in people with CFS/ME even when stimulated with its natural ligand, pregnenalone sulphate, under strictly controlled conditions.

As there are multiple TRP channels and autonomic receptors, we have identified these may also be implicated in this disabling illness.

We have clear evidence from at least two separate studies that these ion channels, as well as calcium and its signalling, are dysfunctional in CFS/ME.

Our team at NCNED is now targeting pharmacotherapeutics to treat this disorder.

NCNED is pleased to acknowledge all our donors and benefactors. Special thanks to the Stafford Fox Medical Research Foundation, Mr Douglas Stutt and the Queensland Government for their unfailing support.

 

[hixxy]

The pubmed links are the same for both papers too and the date has just been updated, so I think it must have been published prematurely.

 

[Gingergrrl]

How would this paper relate to someone having autoantibodies that attack the CA+ channel or a calcium channelopathy? Even the simplified link is above my head! Am trying to figure out if this relates to my situation or is something unrelated. Thanks in advance!

 

[allyann]

I noted this from the press release today:

Our team at NCNED is now targeting pharmacotherapeutics to treat this disorder.

 

[hixxy]

I noted this from the press release today:

They had been planning this since 2015 but didn't get the funding until the end of last year.

 

[Gingergrrl]

I noted this from the press release today:

I looked at the FB Page and wish I could understand it better so am asking for help from a group I belong to for people with my same CA+ autoantibody (except we cover a vast variety of diagnoses and symptoms). Right now the main treatments are things like IVIG, RTX and cancer screenings. But this may be unrelated until I can understand the article better!

 

[Gingergrrl]

Am bumping this thread b/c it links with a new, similar thread that was posted today and hoping that someone can tie the two together and explain how they relate to CA+ Channel autoantibodies. Thanks in advance to all you smart people out there .

 

[allyann]

I looked at the FB Page and wish I could understand it better so am asking for help from a group I belong to for people with my same CA+ autoantibody (except we cover a vast variety of diagnoses and symptoms). Right now the main treatments are things like IVIG, RTX and cancer screenings. But this may be unrelated until I can understand the article better!

I am glad I am not the only one @Gingergrrl that has trouble understanding these papers

 

[M Paine]

For anyone wanting to follow this paper, I'd recommend starting here - Nature 2003 - TRP channels as cellular sensors

Then read this groups earlier paper -> Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

 

[deleder2k]

The pain specialist gave me Verapamil, a non–dihydropyridine calcium channel blocker, to try out to dilate my blood vessels to relieve pain and reduce muscle spasms. I also told him that alcohol improves my symptoms. The doc said I should keep him updated if there is any interesting research. Does anyone understand if this study is related to that drug in any way?? I don't understand any of this.

 

[deleder2k]

I noted this from the press release today:

Do we know what kind of drugs?? I just got a non–dihydropyridine calcium channel blocker called Verapamil to treat pain/ME symptoms.

 

[hixxy]

Do we know what kind of drugs?? I just got a non–dihydropyridine calcium channel blocker called Verapamil to treat pain/ME symptoms.

They haven't released any details of drugs they are looking at.

 

[Gingergrrl]

Does anyone understand if this study is related to that drug in any way?? I don't understand any of this.

I don't understand the study at all and neither do my friends in my CA+ Channel group. I am hoping someone here will interpret it into basic terms for us science dummies .

I can tell you though, that b/c of my CA+ autoantibody, I have been told by Neuros and my main doc not to take any meds that further block the calcium channel. I also do better with vasoconstrictors like Midodrine (which I am back on and in conjunction w/IVIG is really helping me at present). I have complete alcohol intolerance (but this may be due to the histamine levels and a different issue).

So I think you and I are very different in this regard. @deleder2k Am curious and cannot remember, have you been tested for any autoantibodies (like the Anti-Neuronal/Paraneoplastic Abs, Cell Trend tests, etc)?

 

[deleder2k]

Is that ANA? ANA = negative. Haven't done cell trend test..

 

[alicec]

How would this paper relate to someone having autoantibodies that attack the CA+ channel or a calcium channelopathy?

Does anyone understand if this study is related to that drug in any way?? I don't understand any of this.

The study doesn't relate to these questions. It simply shows that there are some differences in response of TRP3 ion channels on NK cells in patients with CFS/ME compared with controls, when these isolated cells are manipulated in the test tube.

This is not likely to be peculiar to NK cells since these receptors are present on many cell types, it's just that they chose to study NK cells.

That is really as far as the study goes. It is an observation. The rest is speculation.

What is the significance of the observation? The authors incline to the idea that it might be causal since they say they have observed differences in SNPs on TRP genes in CFS/ME patients compared with controls.

However that study (and all the SNP studies coming from this group) is very dubious. When they finally did what the should have done from the beginning, namely corrected for multiple comparisons, they found no difference in the various SNPs they had been studying. It is discussed here.

A lot more research is necessary to work out where the observation fits in the overall scheme of things. First do these changes hold up in vivo or are they in vitro artefacts? If they do occur in vivo, is this part of the pathophysiology of CFS/ME or just a downstream consequence of some other problem?

All of that remains to be determined, so don't get too excited yet.

 

[AndyPR]

http://www.techtimes.com/articles/1...-mysterious-reason-traced-to-immune-fault.htm

http://www.iflscience.com/health-an...e-a-defective-channel-in-immune-system-cells/

 

[M Paine]

TRPM3 expression in tissues (https://www.ncbi.nlm.nih.gov/gene/80036/?report=expression)

 

[Gingergrrl]

"TRPM3 is an ion channel, controlling the way calcium ions are transmitted between cells and carrying instructions in the process."

This is a sentence from the second link that you posted above @AndyPR and was wondering if it is the same as the original article or something different? Am still trying to sort out of the role of having the Anti CA+ autoantibody and whether it relates to these articles?

 

[alex3619]

This is not likely to be peculiar to NK cells since these receptors are present on many cell types, it's just that they chose to study NK cells.

I think that is an important point, one I have tried to push. If validated this kind of thing will probably have the greatest impact on the brain, but through circulatory factors it may affect every single tissue in addition to the nearly universal expression of these types of receptors. In other words its about a multisystemic impact.

False positives are a very big risk with this kind of research. I suspect, but haven't seen anything definitive, that the current push is due to additional unpublished findings.