The disabling illness described as either Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME) results in a wide spectrum of symptoms, the most disabling often being a profound lack of energy, muscle pain, headache, and cognitive issues.  The illness is also characterized by an increase in symptoms when in the upright position or following physical activity that would not be challenging to a healthy individual (post-exertional malaise).  The factors that incite and perpetuate the illness are unknown, few treatment options exist, and full recovery is rare.  We have previously investigated the possibility that a member of the murine retrovirus family could be involved.   While that virus has been eliminated as a suspect, the existence of one or more inciting pathogens has not been ruled out.  Well-documented outbreaks of ME/CFS implicate an infectious cause for at least some cases.  Rapid onset following a viral illness has been reported, though many individuals recount a more gradual onset with no clear single provocation.

Immune cells adjust their metabolism when they transition from quiescence to activation due to highly regulated signals indicating a threat.  If metabolic programs at rest and after activation are abnormal, immune cells will not be able to respond adequately.  Dysfunctional response can prevent proper response to a pathogen and contribute to inflammation or autoimmunity.  We are currently investigating fatty acid metabolism in immune cells from ME/CFS patients vs. controls, using both the Agilent Seahorse flux analyzer and flow cytometry.

Previously, we examined glycolysis and oxidative phosphorylation as well as mitochondrial membrane potential in two types of T cells.  This work demonstrated abnormalities in both types of T cells.  We are carrying out additional studies of various types of T cells, B cells, and natural killer cells.

Plasma contains a multitude of signaling proteins, especially ones involved in communication between immune cells or between tissues and immune cells. Plasma proteins may also provide insights into the function and stresses affecting tissue and organs.  We have carried out a pilot study with 20 female ME/CFS patients and 20 controls using Somascan technology from Somalogic, which allowed us to study the relative abundances of 4790 unique proteins in plasma.  Our published work describes the detection of abnormalities in the ephrin-eph pathway in ME/CFS.  This pathway is involved in many biological processes such as axon guidance, angiogenesis, and epithelial cell migration.  Furthermore, we detected dysfunction of immune signaling.  The study indicated that combinations of plasma proteins may be able to serve as biomarkers of the disease.

The ratio of the protein EPHA5 and CFTR gives a high level of discrimination between ME/CFS patients and controls, according to ROC analysis.  Both of the proteins are involved in regulation of neurotransmitter release in response to varying blood glucose concentrations.