Exosome-associated Mitochondrial DNA is Elevated in Patients with ME/CFS and Stimulates Human Cultured Microglia to Secrete IL-1β

Abstract

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise and cognitive problems. The pathogenesis of ME/CFS is presently unknown and serum levels of potential biomarkers have been inconsistent. Methods: Exosomes were purified from serum obtained from patients with ME/CFS before and after exercise and their content of mitochondrial DNA (mtDNA) was determined by quantitative PCR. Exosomes from both patients and controls were incubated with cultured human microglia and release of interleukin-1beta (IL-1β) was measured by ELISA.Results: Here we show that serum mtDNA, associated with exosomes, is increased in ME/CFS after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant secretion of IL-1β from cultured human microglia. Conclusion: These results provide evidence for a potential novel pathogenetic factor and target for treatment of ME/CFS.

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

“…The second study assessed circulating mitochondrial DNA (mtDNA) levels associated with exosomes in response to physical exercise. The exosomes from patients with and without ME/CFS were incubated with a human microglial cells and release of IL-1β was measured ( Theoharides et al, 2021 ). The analysis showed that after exercise exosome-associated mtDNA was increased in patients with ME/CFS but not controls and that in cell culture there was significantly increased secretion of IL-1β from microglial cells.…”