Red blood cell biomechanics in Chronic Fatigue Syndrome, by Amit K Saha, Brendan R Schmidt, Arun Kumar, Amir Saadat, Vineeth C Suja, Vy Nguyen, Justin K Do, Wendy Ho, Mohsen Nemat-Gorgani, Eric SG Shaqfeh, Anand K Ramasubramanian, Ronald W Davis in Summer Biomechanics, Bioengineering and Biotransport Conference papers, June 25 -28, Seven Springs, PA, USA, SB3C2019-221 [Published July 1, 2019]
Chronic Fatigue Syndrome (CFS) is a multi-systemic illness of unknown etiology, affecting millions worldwide, with the capacity to persist for several years. It is characterized by persistent or relapsing unexplained fatigue of at least 6 months’ duration that is not alleviated by rest.
CFS can be debilitating, and its clinical definition includes a broad cluster of symptoms and signs that give it its distinct character, and its diagnosis is based on these characteristic symptom patterns including cognitive impairment, post-exertional malaise, unrefreshing sleep, headache, hypersensitivity to noise, light or certain food items.
Although an abnormal profile of circulating proinflammatory cytokines, and the presence of chronic oxidative and nitrosative stresses have been identified and correlated with severity in CFS, there are no reliable molecular or cellular biomarkers of the disease.
In the present work, we focus on the pathophysiological changes in red blood cells (RBCs) since CFS is a systemic disease rather than of a particular organ or tissue, and RBCs, comprising ~45% of blood volume, are responsible for microvascular perfusion and tissue oxygenation.
RBCs deform and travel through microvessels smaller than their diameter to facilitate the optimal transfer of gases between blood and tissue. The usual shape of a RBC is a biconcave discoid, which is changed to an ellipsoid due to shear flow. This shape gives them a specific surface area-to-volume ratio which facilitates large reversible deformations and elastic transformation .
We used a high throughput microfluidic platform to assess the changes in RBC deformability between CFS patients and matching healthy controls. We also performed computational studies to have a better understanding of the cell deformation. In order to explore the mechanisms for observed changes in cell deformability, we explored the membrane fluidity, reactive oxygen species, and surface charge, of RBCs.
Erythrocyte deformability refers to the ability of erythrocytes (red blood cells, RBC) to change shape under a given level of applied stress, without hemolysing (rupturing). Wikipedia
Together, the various estimates show that the RBCs in CFS patients are significantly less deformable than those of healthy controls. We speculate that the larger and less deformable RBCs in CFS patients may partly explain the musculoskeletal pain and fatigue in the pathophysiology of CFS due to impaired microvascular perfusion and tissue oxygenation.
It has been shown that the quality of life of ME/CFS patients was significantly worse as compared to patients with diseases like sclerosis, cancer (multiple types, such as colon, breast and prostate), type II diabetes, rheumatoid arthritis and chronic renal failure, among others.
This work introduces a new paradigm in our understanding of the mechanistic aspects of ME/CFS. It also opens the possibility of a diagnostic platform for ME/CFS using RBC deformability as the biomarker.