1) Interesting presentation by Anouk Slaghekke at the 2025 Berlin conference.
This Dutch team found that small blood vessels of patients with ME/CFS and Long Covid are clocked up with Collagen IV.
2) They zoomed in on the muscle capillaries, the tiny blood vessels that are so small that red blood cells need to move through them one by one.
3) The Dutch researchers found that the basement membrane was thicker in patients.
This is the supportive layer of proteins around the capillaries. It consists of proteins such as Collagen IV. Too much of it can stiffen the capillary walls.
4) They also found that the lumen space (the open space inside a blood vessel where blood actually flows) was reduced.
This may affect the perfusion of oxygen and nutrients to the muscle site.
5) Using electron microscopy the researchers could zoom in even further. This confirmed basement membrane thickening as well as membrane reduplications and signs of endothelial activation.
The endothelial cells were full of vesicles, excreting things into the circulation.
6) There was not a lot of overlap between patients and controls on these markers, so the researchers are exploring if they have potential as a biomarker or diagnostic test. They are looking for validation cohorts from other groups to see if they see similar things there.
7) The presentation by Ph.D researcher Anouk Slaghekke can be viewed on the website of the ME Research Foundation (@MECFSResearch). events.mecfs-research.org/en/events/conf…
They found that red blood cells from ME/CFS patients are slower and less responsive to low oxygen levels in a lab device that mimics small blood vessels.
2) Previous studies suggested that red blood cells change their shape more easily when oxygen is low. That allows them to move faster through small blood vessels (capillaries) and deliver oxygen where it is needed.
3) The red blood cells of ME/CFS patients do this as well, but they are less responsive to lower oxygen levels.
At normal oxygen levels (normoxia with partial oxygen pressure of 20-60 mmHg), they flowed as fast, or even faster, as those from healthy controls.
1) Interesting experiment on fatiguability of arm muscles that might be useful as an objective test.
During repeated handgrip tasks, researchers found that "the neuromuscular system experienced changes earlier than the actual behavior"
2) The experiment used multiple fatigue measures during the task:
– EMG = tiny electrical signals in the forearm muscles
– EEG = brain waves at the scalp
– fMRI = brain activity through blood oxygenation levels
– contraction force of the muscle
– a subjective fatigue scale.
3) These all showed the expected signs of fatigue:
- EMG shifted from high to low frequencies and more recruitment of motor units.
- EEG had increased power in multiple frequency bands
- fMRI showed an increase in the blood oxygen in the cerebellum.
1) In a new preview video, Dr. Yarred Younger from the University of Alabama says he found evidence that ME/CFS patients have more microglia cell activation in their brains than healthy controls.
His theory is that chronic brain inflammation is driving symptoms in ME/CFS.
2) A short recap of the evidence:
In a 2014 paper researchers, Japanese researchers reported neuro-inflammation in ME/CFS using PET-scans. pubmed.ncbi.nlm.nih.gov/24665088/
1) In a new pre-print, the lab of Bhupesh Prusty reports that antibodies (IgG) from ME/CFS patients cause mitochondrial fragmentation in endothelial cells.
This was not seen in antibodies from MS patients or healthy controls.
2) Their experiments were inspired by two studies finding ME/CFS and long COVID-like symptoms in mice after transferring IgG from patients.
3) Prusty's team purified IgGs and exposed them in the lab to two cell types, foreskin fibroblasts and endothelial cells. Only in the latter was IgG able to enter the cells.
1) Saw some skepticism about DecodeME, asking if it is overhyped.
As an account that focuses on dissecting and critically analyzing research (our name was 'ME/CFS Skeptic' for a reason!), we think it’s the real deal.
Here are a couple of reasons why it stands out. 🧵
2) First, there is the sample size: 15.000 participants dwarfs any other ME/CFS study in comparison. Try finding biomedical ME/CFS studies with more than 1000 participants: there are almost none...
3) Some ME/CFS studies use big sample sizes but only because they extract them from an already existing database, such as electronic health records or an external biobank.
These usually have poor info on ME/CFS with big uncertainties about case selection.
1) The DecodeME study compared DNA of ca. 15,000 ME/CFS patients and 250,000 controls and found significant differences in 8 regions of our genome.
The Manhattan plot below shows the genes and chromosomes involved.
Let’s unpack the results 🧵
2) A first major finding is that the results for females and males were very similar.
This was a surprise, as some had expected the biological pathways behind ME/CFS to differ between males and females. Not so!
3) ME/CFS is much more common in women (84% of ME/CFS participants were female), but the millions of DNA variants analyzed didn’t provide an answer of why this is the case.
The sex chromosomes weren't analyzed yet, so this is likely where the answer for the sex difference lies.