ME/CFS Science Profile picture
Aug 17 10 tweets 3 min read Read on X
1) 🩸 New paper by the team of Ronald Davis.

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. Image
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.
4) But when oxygen levels were lowered (hypoxia with oxygen pressure of 0-12 mmHg), the blood cells of ME/CFS patients were less able to increase their speed, making them slower than red blood cells from controls.
5) Figure 1.B below shows the main findings. What differentiated ME/CFS patients was not so much the speed of the cells itself as the change in speed in response to oxygen tension.

You can see that the green slope of patients is much flatter. Image
6) The authors think this might help explain the cerebral blood flow problems that have been reported in ME/CFS. Poor oxygen delivery also plays a role in many theories of ME/CFS, including those on endothelial dysfunction and exercise intolerance.
7) Davis his team used machine learning to differentiate ME/CFS patients and controls. Their best model reached an accuracy of 77.8% and an AUC of 0.82.

(We have some doubts about how useful these metrics are...) Image
8) Lastly, the authors tested two drugs, Salmeterol and Xanomeline, that are used to treat asthma and schizophrenia, respectively, and increase red blood cell deformability.

It seems that xanomeline worked the best at increasing RBC speed and responsiveness.
9) A caveat is that this was a small study with only 35 ME/CFS patients and 23 controls. These were not fully matched for sex (71% vs 60% females, although this didn't affect the slopes). They also found no difference between moderate and moderate-severe ME/CFS patients.
10) Link to the study (open-acces):

Gua et al. 2025. Microfluidic assessment of PO2-regulated RBC capillary velocity in ME/CFS
sciencedirect.com/science/articl…

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More from @mecfsskeptic

Aug 17
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" Image
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.
Read 10 tweets
Aug 14
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. Image
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/

A Dutch 2022 paper, however, found no difference between patients and controls
pubmed.ncbi.nlm.nih.gov/34815320/
3) Both were small studies with only 9 ME/CFS patients and they used an older and not so sensitive tracer ([¹¹C]-(R)-PK11195).

Younger got NIH funding for PET scans with a better, second-generation, ligand (18F-DPA-714)
reporter.nih.gov/project-detail…
Read 10 tweets
Aug 14
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. Image
2) Their experiments were inspired by two studies finding ME/CFS and long COVID-like symptoms in mice after transferring IgG from patients.

One from the Dutch team of Eijkelkamp/Den Dunnen:
biorxiv.org/content/10.110…

And one from the US group of Iwasaki:
biorxiv.org/content/10.110…
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.
Read 11 tweets
Aug 10
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. 🧵 Image
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.
Read 20 tweets
Aug 7
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 🧵 Image
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.
Read 24 tweets
Aug 2
1) Spanish researchers exposed muscle cells to serum of ME/CFS and Long Covid patients and found:

- reduction in muscle contraction strength

- upregulation of genes involved in protein translation

- elevated oxygen consumption Image
2) It looks like the 'something in the blood' hypothesis is back on the table: serum of patients caused cellular stress that serum of healthy controls did not.

The sample size was really small though: serum of only 4 ME/CFS patients and 5 Long Covid patients was used.
3) The researchers developed 3D skeletal muscle tissue in the lab and exposed it for 48 hours to sera of patients (ME/CFS and LC patients) or controls. They replicated the experiment a couple of times per serum sample (these are probably the white open dots in the graphs).
Read 10 tweets

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