Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome, Saha et al, 2019

[SNT Gatchaman]

Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome
Amit K. Saha, Brendan R. Schmidt, Julie Wilhelmy, Vy Nguyen, Abed Abugherir, Justin K. Do, Mohsen Nemat-Gorgani, Ronald W. Davis
Clinical Hemorheology and Microcirculation 71 (2019) 113–116
DOI: 10.3233/CH-180469
Full Text Link

Abstract
BACKGROUND: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.

METHODS: We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.

RESULTS AND CONCLUSION: We observed from various measures of deformability that the RBCs isolated from ME/ CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test.

Edit: We have 3 threads on related or the same research by the same team:
Erythrocyte Deformability As a Potential Biomarker for Chronic Fatigue Syndrome, Davis et al (2018)
Altered Erythrocyte Biophysical Properties in Chronic Fatigue Syndrome, 2019, Saha, Davis, et al
Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome, Saha et al, 2019

 

[SNT Gatchaman]

We speculate that the larger and less deformable RBCs in ME/CFS patients may partly explain the musculoskeletal pain and fatigue in the pathophysiology of ME/CFS due to impaired microvascular perfusion and tissue oxygenation. Of note, it was previously reported that no significant difference in average deformability was observed between erythrocytes obtained from healthy controls and ME/CFS patients, as measured by ektacytometer. This apparent contradiction can be because of the lower sensitivity of the ektacytometer, which reports the deformability based on time and population averages indirectly from light scattering, while as seen from this work, the deformability is best measured directly on an individual cell basis.

 

[hibiscuswahine]

Very interesting part of the puzzle, spent 14% more time in the channels and 18% slower due to being “unusually bigger” with 15% less elongation so stiffer. And RBC do alter their shape with oxidative stress and inflammation and there might be a further impact from the disease process (still to be confirmed…) and which would tie in with a chronic relapsing condition and gradual worsening of overall function or other trajectories. Also meds and supplements not known to cause these changes so some nice contributory evidence towards the microcirculation/perfusion enquiry…and does this oxidative stress/inflammation of the RBC alter the offloading of oxygen to the cell/tissue?

 

[SNT Gatchaman]

does this oxidative stress/inflammation of the RBC alter the offloading of oxygen to the cell/tissue?

It sounds as if it have some effect. Also the Stanford researchers recently said that ME RBCs were much less deformable when hypoxic (unlike normals), which could act to produce positive feedback perpetuation.

It's possible it increases tissue oxygenation (somewhat paradoxically). Please see this post where I talked about a possible two-state mechanism.

ETA: ah think you'd already seen it - sorry

 

[Hutan]

At one point, Ron was backtracking from the finding in this paper. And then, earlier this year he suggested the work may in fact be correct.

Ron Davis also suggests in that video that the earlier work on red blood cell deformability may be correct. He says that the later work done which found no difference in RBC deformability between blood from people with ME/CFS and healthy controls may have been confounded by the time taken to get the samples analysed (longer in the later studies), and differences in the treatment of the blood. Changes in the oxygenation of the cells was one variable mentioned.

We used a custom microfluidic platform and high-speed microscopy

I recall from something I think @SNT Gatchaman posted that assessing red blood cell deformability is regularly done and that there are existing techniques to do it. Which made me wonder why the Davis team had chosen to make a custom technique when doing exploratory work in ME/CFS. Maybe Brendan Schmidt's thesis explains why they didn't first start by using an established technique.

 

[Mithriel]

When Dr Simpson first found badly shaped RBCs his research was not replicated. He complained that he examined cells as soon as they were removed from patients but the replication studies all stored the cells until they looked at them. This storage process restored the cells to their proper shape.

As usual with ME, nothing was resolved one way or another.

It is interesting that it keeps cropping up.

I have problems with my fingernails and the tips of my fingers which hypoxia would explain.