Neutrophil issues

Looks like a nice relatively simple diagnostic test. I really don't care if it shows up in other diseases, it just shows there is a common thread to do with fatigue or autoimmunity, its the symptoms combined with the objective test that identifies any disease anyway. I hope they get this one to a usable point (unlike the nanoneedle).
 
Braganca said:
Is the OMF neutrophil study different and separate to Michael Van Elzakkers neutrophil study?
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From what I can see, they are totally separate studies. Unfortunately Michael doesn't seem to be sharing exactly what they will be looking for, he says on twitter that he has learned to not openly share as much as he used to. He does say that some of the members of the team previously produced this paper
Neutrophil Profiles of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children
so perhaps they will look at the same things in the ME/CFS neutrophils.


On the study in Ron's lab on ME/CFS neutrophils - from the above video:
OMF are funding the study.
Ron says that when neutrophils get to sites with bacteria, they explode, with their cell contents forming net traps that capture bacteria - we've discussed those on the forum. This tendency to explode makes separating them a bit difficult, centrifuging can damage them. They are developing a microfluidic device that has the blood run in channels with the neutrophils adsorbed.

A person in Ron's lab (Vanessa, her surname was not mentioned) initiated the neutrophil work and continues to work on this. she has looked at how fast neutrophils move across a surface towards a site of simulated infection. She found that neutrophils are 'much slower' than healthy neutrophils. Ron says 'it might be a diagnostic test'. 'We just have to measure a number of them to make sure we get good reproducibility'. Ron did not say how many samples have been looked at so far. (Is anyone aware of any communication from Vanessa about her work?)

Ron thinks that the innate immunity is stuck 'on' in ME/CFS. He says this aligns with the itaconate shunt hypothesis - the itaconate shunt is turned on when the innate immunity system is activated. It reduces the body's ability to produce ATP.

Intuitively, the idea of an immune system that is permanently 'switched on' appeals to me - it could fit with some people actually having smouldering infections and others just having a faulty switch, all ending up in the same ME/CFS place. However, I don't think Ron explained why the innate immunity being stuck on would result in the neutrophils moving slower. It's arguable that having an activated innate immunity would make the neutrophils move faster, not slower. I'm not sure if the idea is that the neutrophil itself isn't making enough ATP for it to function properly? I don't know - I didn't hear the logic of the connection being explained.

As usual, there was quite a bit of optimistic talk about the latest idea for a biomarker, and forthcoming treatments.
 
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I'm not sure why Ron is making it sound as though a microfluidic device to assess neutrophil movement is a new thing, or why it needs to be developed.

For instance, there was this 2013 paper:
Measuring neutrophil speed and directionality during chemotaxis, directly from a droplet of whole blood
Anh N Hoang, Caroline N Jones, Laurie Dimisko, Bashar Hamza, Joseph Martel, Nikola Kojic, Daniel Irimia
"To address the need for rapid and robust assays, we designed a microfluidic device that measures neutrophil chemotaxis directly from a single droplet of blood."

Here's another one:
A real-time assay for neutrophil chemotaxis 2016
"Here we report a rapid, non-invasive, impedance-based, and label-free assay for real-time assessment of neutrophil chemotaxis."

In 2016, there was even a competition, essentially a neutrophil race
A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells
"These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses."
"The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis"

(I note that one of the authors of the 2021 paper that Michael Van Elzakker gives as an example of past work by his current collaborators
Neutrophil Profiles of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children 2021
.... Daniel Irimia,7)
is also an author of that 2013 paper. So, there's a good chance that the team working with Van Elzakker on characterising neutrophils in ME/CFS has solid knowledge.
 
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Hutan said:
From what I can see, they are totally separate studies. Unfortunately Michael doesn't seem to be sharing exactly what they will be looking for, he says on twitter that he has learned not to openly share as much as he used to. He does say that some of the members of the team previously produced this paper
Neutrophil Profiles of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children
so perhaps they will look at the same things in the ME/CFS neutrophils.


On the study in Ron's lab on ME/CFS neutrophils - from the above video:
OMF are funding the study.
Ron says that when neutrophils get to sites with bacteria, they explode, with their cell contents forming net traps that capture bacteria - we've discussed those on the forum. This tendency to explode makes separating them a bit difficult, centrifuging can damage them. They are developing a microfluidic device that has the blood run in channels with the neutrophils adsorbed.

A person in Ron's lab (Vanessa, her surname was not mentioned) initiated the neutrophil work and continues to work on this. she has looked at how fast neutrophils move across a surface towards a site of simulated infection. She found that neutrophils are 'much slower' than healthy neutrophils. Ron says 'it might be a diagnostic test'. 'We just have to measure a number of them to make sure we get good reproducibility'. Ron did not say how many samples have been looked at so far. (Is anyone aware of any communication from Vanessa about her work?)

Ron thinks that the innate immunity is stuck 'on' in ME/CFS. He says this aligns with the itaconate shunt hypothesis - the itaconate shunt is turned on when the innate immunity system is activated. It reduces the body's ability to produce ATP.

Intuitively, the idea of an immune system that is permanently 'switched on' appeals to me - it could fit with some people actually having smouldering infections and others just having a faulty switch, all ending up in the same ME/CFS place. However, I don't think Ron explained why the innate immunity being stuck on would result in the neutrophils moving slower. It's arguable that having an activated innate immunity would make the neutrophils move faster, not slower. I'm not sure if the idea is that the neutrophil itself isn't making enough ATP for it to function properly? I don't know - I didn't hear the logic of the connection being explained.

As usual, there was quite a bit of optimistic talk about the latest idea for a biomarker, and forthcoming treatments.
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@Jonathan Edwards Thoughts on the innate immune system being stuck "on" in ME? Does the current evidence allow this or would we see abnormalities the patients do not have? I too feel on a subjective level that it makes sense but i would think we would have figured it out by now if it was that easy. And, shouldn't steroids help at least a little bit? I have tried high dose methylprednisolone and it only made me worse (I've also tried other kinds of cortisone and they never helped)
 
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Jaybee00 said:


The neutrophil study
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Listening to this gave me an eerie sense of déjà vu - or maybe déjà entendu, given I have to listen with eyes closed. Anyway, it feels like the nano-needle all over again. Some highly intriguing early findings of differences between ME and HC. An intuitive explanation but not enough detail to judge how much sense it really makes. Then all the focus immediately moves to developing a device that's cheap and easy to use. Which feels back to front to me.

Having cheap and easy-to-use devices or tests is of course essential for maximising patient access to any future biomarker. However, given that there already are ways to assess how fast neutrophils move, the logical next step now would be to use those existing methods to test if the early findings hold up in larger cohorts and how they compare to disease controls.

If the findings really turn out to be solid, that's the time to think about making better devices. But right now I'd much prefer to learn as quickly and as conclusively as possible if there is anything wrong with our neutrophils or not, I don't want to wait... and wait... and wait for a new device first (nano-needle anyone?)

As a potential bonus, if you start with gathering some really good evidence for a biomarker - neutrophils or impedance or whatever - using research lab tech, it's likely outside funding could be attracted for developing a better clinical lab device or test at that stage, too, even if the aim is a cheap device. The sheer numbers of potential patients - not just ME, think how many pwLC would want to know if they've acquired ME - would still make it an attractive enough proposition for investors. But they'll want some convincing data first.
 
Ravn said:
Anyway, it feels like the nano-needle all over again. Some highly intriguing early findings of differences between ME and HC. An intuitive explanation but not enough detail to judge how much sense it really makes. Then all the focus immediately moves to developing a device that's cheap and easy to use. Which feels back to front to me.
Click to expand...
:thumbup:
 
Hubris said:
@Jonathan Edwards Thoughts on the innate immune system being stuck "on" in ME? Does the current evidence allow this or would we see abnormalities the patients do not have? I too feel on a subjective level that it makes sense but i would think we would have figured it out by now if it was that easy.
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I think vague ideas like that are unhelpful. What we need are hard direct facts like that neutrophils go slower and certain conditions are whatever. You then look for a specific mechanism for that. Immune systems are not 'on' or 'off' any more than a price force is on or off but it may be searching too many innocent people.

Neutrophil movement, both just speed (chemokinesis) and directional movement (chemotaxis) where extensively studied in the 1970s. Standard techniques were available. I do not see why there would be a need for a new microfluidic device.
 
More on Dr Merete Long (the Dundee researcher) who was given an award for her work on neutrophils in Long Covid:

https://www.dundee.ac.uk/stories/prestigious-award-university-researchers-covid-19-work
PREDICT-COVID19, the study led by Merete, looked at cellular changes occurring within neutrophils in patients with Covid-19. Results showed that changes within neutrophils were linked to delayed recovery and highlighted neutrophils as potential therapeutic targets in long Covid.

Forum thread here on the study:
Altered neutrophil proteomes in COVID19 patients ... associated with delayed recovery: ... PREDICT-COVID19, 2022, Long et al
 
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