Center for Enervating NeuroImmune Disease

The profound fatigue experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has led to the theory that energy metabolism may be dysregulated. Discordant results have been obtained in prior studies of mitochondrial and metabolic function.

Differences in between various properties of lymphocytes in ME/CFS cases and controls have been documented, but the basis of the alterations is not understood. Lymphocytes require both glycolysis and oxidative phosphorylation to carry out their immune functions. Usage of these two primary pathways for energy generation is known to change between resting and activated cells in healthy individuals, and to differ between lymphocyte type. Impaired functioning or improper regulation of energy metabolism in lymphocytes could be either the cause or consequence of the unknown damage to cellular processes that occurs in ME/CFS.

In order to investigate the efficiency and usage of glycolysis and mitochondrial respiration in ME/CFS immune cells, Maureen Hanson’s group has assayed leukocytes from blood samples collected by Susan Levine, M.D. Three types of immune cell, B, T, and NK cells, were separated using a magnetic bead method and then analyzed with the use of an Agilent/Seahorse flux analyzer. This project is supported by an NIH NIAID exploratory grant, R21 AI117595.

These experiments have provided measures of basal respiration rate, maximal respiration rate, ATP synthesis rate, spare respiratory capacity, basal glycolysis rate, maximal glycolysis rate, and glycolytic reserve in immune cells before and after stimulation. This study has revealed alterations in immune cell function in ME/CFS due to abnormal metabolism¹. Detection of abnormalities in energy generation also has implications for the basis of other symptoms of ME/CFS. Alexandra Mandarano, lead investigator, has created a video describing the findings. In addition, graduate student Jessica Maya is continuing this work to investigate fatty acid oxidation in immune cells. Jessica has described some of this work in a brief video.

1. Mandarano AH, Maya J, Giloteaux L, Peterson DL, Maynard M, Gottschalk CG, Hanson MR. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. 2020 Mar 2;130(3):1491-1505.