In August, OMF researchers from our collaborative centers at Stanford University and Montreal published a couple of papers investigating red blood cell movement and correlating a plasma marker to symptom profiles. I want to, of course, share these two publications with you all, but also try to draw some connections between the two studies that might not be immediately obvious.
The Heart of the Matter
- Paper from OMF Collaborative Center at Stanford: Found that people with ME/CFS have red blood cells (RBCs) that move slower through capillaries when oxygen levels (PO2) are low.
- Paper from OMF Collaborative Center at Montreal: Found that low levels of fibroblast growth factor 21 (FGF-21) is linked to more severe post-exertional malaise (PEM) in people with ME/CFS. High levels of FGF-21 are associated with better cognitive function.
- Drawing connections: Low PO2 and problems with mitochondria can lead to both slower RBC movement and changes in FGF-21 levels. The combination of these factors seem to be connected to different ways ME/CFS symptoms show up in patients.
Microfluidic Assessment of PO2-Regulated RBC Capillary Velocity in ME/CFS
This paper explored red blood cell (RBC) velocity in microfluidic capillaries at different oxygen tensions (PO2). They found that at reduced PO2 (low levels of oxygen in the blood), RBC velocity was impaired for people with ME/CFS. Ultimately, this result shows potential as a way to diagnose ME/CFS and test treatments’ abilities to improve RBC velocity.
Read the full publication in Blood RCI.
Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia
This paper investigated fibroblast growth factor 21 (FGF-21) levels in ME/CFS and fibromyalgia, correlating them to symptom burden and cognitive function. In this study, they found that low levels of FGF-21 correlated to increased post-exertional malaise (PEM) severity and immune/autonomic symptoms in ME/CFS. High levels of FGF-21 correlated with better cognition but more fatigue in ME/CFS. In the future, these results may help yield clinically meaningful subtypes to guide precision medicine.
Read the full publication in the International Journal of Molecular Sciences.
The Bigger Picture
Upon first look, these two studies are seemingly disconnected, so how do they fit together within the bigger picture of ME/CFS? Reduced PO2 can stimulate FGF-21 production as a stress response. FGF-21 can impact cerebral blood flow and broader microcirculation through its action on vascular endothelial cells. Impaired RBC capillary velocity can in turn exacerbate issues with oxygen delivery and can therefore contribute to PEM. In addition, FGF-21 is a marker of mitochondrial dysfunction, which is also linked to RBC deformability.
So taking these two studies together, we can try to draw some connections from PO2 and mitochondrial dysfunction to FGF-21 levels and RBC capillary velocity to different symptom profiles. In this case, we might consider reduced PO2—perhaps a result of impaired oxygen extraction—and/or mitochondrial dysfunction as triggers for impaired RBC capillary velocity and changes in FGF-21 levels. People that produce higher levels of FGF-21 as a result might be able to partially compensate for the reduced RBC capillary velocity with improved cerebral blood flow that correlates to their better cognition. But those with lower levels of FGF-21 may not have that ability, resulting in more severe PEM.
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