Guo et al. (2025)
- Authors: Yaojun Guo, Sitong Zhou, Samuel Ren, Xin Liu, Mohsen Nemat-Gorgani, Mike Gresser, Ronald W. Davis, Jiandi Wan
- Institutes: Department of Chemical Engineering, University of California, Davis; Department of Pathology and Lab Medicine, Medical Center of University of California, Davis; Henry Gunn High School.
- Publisher: blood RCI
- Link: DOI
Summary
This research provides a potential physical explanation for the blood flow abnormalities and oxygen delivery problems often reported in ME/CFS. It suggests that the red blood cells themselves are less able to respond to the body’s demand for oxygen, which could contribute to symptoms like post-exertional malaise and cognitive dysfunction. The “velocity slope” measurement developed in this study is a promising candidate for a much-needed objective diagnostic biomarker for ME/CFS. Furthermore, the in vitro success of two existing drugs in correcting this RBC dysfunction offers a new, targeted avenue for the development of future treatments aimed at improving microcirculation, though these findings are preliminary and require much more research.
What was researched?
This study investigated how red blood cells (RBCs) from individuals with ME/CFS change their speed in tiny, capillary-like channels in response to varying oxygen levels (). The researchers explored whether these measurements could serve as a diagnostic biomarker for ME/CFS and be used to evaluate the effects of potential therapeutic drugs.
Why was it researched?
Previous research has consistently shown that ME/CFS patients have impaired cerebral blood flow (CBF), but the underlying cause is unclear. Based on prior findings that RBCs actively regulate capillary blood flow in response to local oxygen demand, the researchers hypothesized that RBC function might be compromised in ME/CFS, contributing to these blood flow abnormalities. This study aimed to test that hypothesis by directly measuring RBC behavior under controlled oxygen conditions.
How was it researched?
This was an ex vivo laboratory study using microfluidic devices to mimic blood capillaries. The researchers analyzed blood samples from a cohort of 35 ME/CFS patients and 23 healthy controls. They measured the velocity of isolated RBCs as they passed through the micro-channels at four different oxygen tensions (), from normal to hypoxic levels. The resulting data were analyzed using statistical methods and machine learning algorithms to assess their diagnostic potential. The team also incubated RBCs from ME/CFS patients with two drugs to see if their function could be improved.
What has been found?
The study found that RBCs from ME/CFS patients have an impaired response to low oxygen. While healthy RBCs sped up significantly as oxygen dropped, ME/CFS RBCs showed a much smaller increase in velocity. The “velocity slope,” which measures this sensitivity to oxygen changes, was significantly lower in the ME/CFS group and proved to be a robust biomarker. A machine learning model using this slope feature was able to distinguish ME/CFS patients from healthy controls with high accuracy (77.8%), sensitivity (76%), and specificity (90%). Additionally, treating ME/CFS RBCs with salmeterol xinafoate 💊 and xanomeline 💊 improved their velocity in response to low oxygen in this lab setting.
Discussion
The authors note that the impaired RBC response to low oxygen may be caused by known cellular issues in ME/CFS, such as reduced RBC deformability and increased oxidative stress. They highlight that dynamic measurements, like testing the response to a stressor like hypoxia, appear more effective for diagnosis than static measurements. The primary limitation acknowledged in the paper is the relatively small sample size, which necessitates further validation in larger patient cohorts.
Conclusion & Future Work
The authors conclude that RBCs from ME/CFS patients exhibit significantly impaired capillary velocity in response to reduced oxygen levels, revealing a previously unrecognized role for RBCs in the disease’s pathophysiology. This RBC-based microfluidic method presents a novel and potentially effective approach for ME/CFS classification and assessment. The research is ongoing with plans to continue with a larger patient cohort to improve the detection accuracy and ease of use.