Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers...ME/CFS 2019, Eguchi et al

Why? I actually doubt it is genetic as well, but I am curious as to why you make this statement. It seems that almost once a month a new genetic marker is stumbled upon that suggests a form of channelopathy, so, I'm curious as to why you say this?

Agreed, except I'm unclear how it works other than theory. My hands-on experience is limited to genetic PP

Sorry, I no longer remember. I know it had something to do with the fact it dealt with skeletal muscles, but that's all I can eek out of my brain.

 

People get ME in outbreaks. It may be that only people with a certain HLA type get ME after an infection because each HLA type is fairly common but the genetic causes of the channelopathies we know about are just too rare.

 

Some people get ME in outbreaks. Many with ME are not part of any known outbreak.

The operative phase here is "we know about". We are learning more about channelopathies all the time. It could be that some are triggered by insults such as infections; maybe not. Ultimately, what is rare relative to channleopathies is our insight.

But I get your point.

 

There may be many paths to ME but since we know it can happen in outbreaks it means that any cause must explain that.

To clarify, I believe that a channelopathy is a plausible cause for ME. To exclude the possibility because people with ME do not have a genetic problem in the DNA they were born with makes no sense since, as you say, we do not know that channelopathies can not be caused by acquired problems.

It was the same with mitochondrial diseases just a few years ago. They said that they could only be caused by inherited defects in the DNA but I believe that has changed.

 

I don't think that's quite accurate. As you say, there may be many paths to ME; some of those paths may not have to lend themselves to outbreaks, e.g., be contageous, or have a shared trigger like mass trial vaccine. Some clearly would.

I wonder if in the early days of reporting MS there were any outbreaks. Probably not, just musing aloud.

Well, I know of at least one former member here who appears to have an acquired channelopathy due to autoantibodies. I belong to a private, vetted channelopathy email community, and everyone there has a PP of some sort, but I cannot recall if anyone discusses how they got it outside of genetic biomarkers. I'm sure this happen, I just forget. I absolutely know some do NOT have genetic markers, so their's is a clinical diagnosis, but I cannot recall more than that - likely because my wife's PP is genetic, so my focus rests there.

 

One of the issues with calcium channel changes is changes to intracellular calcium. If there are any it might mess with the calcium-cyclic AMP balance, effectively causing an intracellular hormone shift that can profoundly change cell function, for better or ill, though more likely a mixture of both. We need to know more about intracellular ionized calcium, not just calcium channels.

 

Thank you very much for your reply.

 

I'm not sure what you mean by 'early days', but there were outbreaks here near where I live and another Canadian city.

 

Wow. Very cool!

I should not have qualified early days. That was poorly worded. I should have said have there ever been indications of MS outbreaks, or the such.

For those who think MS is an immune dysfunction of sorts, or auto-immune, how would they explain this, I wonder?

 

@duncan

The interesting part in the article is that Jacques was diagnosed with MS in 1991, this was the year I became ill with a sudden viral infection that developed into M.E. We live in the same city, but not in the same neighbourhood.

 

I wonder how old the lead's on this paper are. I ask because it reads to me as a bit of a story.

1) Junior Lead - Hey other people are looking at EV's in CFS. Let's see what we can find.
2) Junior Lead - Wow we found something.
3) PhD Adviser - "you should get more people"
4) Junior Lead - Recruit more people and repeat
5) PhD Adviser - "you should get more people"
6) Junior Lead - Recruit more people and repeat
7) PhD Adviser - "you should figure out what is in them"
8) Junior Lead - does analysis - we found some difference's
9) PhD Adviser - "cool - can you differentiate between CFS and other issues" (which I believe was a criticism of other people trying to come up with blood tests at Stanford)
10) Junior Lead - finds yet more people - analyzes again (runs out of money and time) - can tell the difference
11) PhD Adviser - you should publish

If you look at it as a study that was planned from the start, it does come across as a bit dodgy. If you instead read it as a narrative, in which something was found and then they followed up and found more (and perhaps some parts that are more interesting) it is way more interesting (and my mind more likely as to what occurred).

The idea that this is a narrative is also backed up by the language in the paper "led us to further investigate whether assessing EV cargo would lead to the discovery of", "we further explored", etc.

I also feel that some of the negative comments here are again a bit harsh. Would you rather that they sat on this data and waited until it was perfect or published what they had so far (given their likely constraints in terms of both time and money)?

It will be most interesting to see if others can replicate the contents of the EV's using a larger sample size.