Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study

• Published in: PloS one Vol. 17; no. 8; p. e0272703
• Main Authors: Jahanbani, Fereshteh, Maynard, Rajan D, Sing, Justin Cyril, Jahanbani, Shaghayegh, Perrino, John J, Spacek, Damek V, Davis, Ronald W, Snyder, Michael P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.08.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Apoptosis; Bioenergetics; Biology and Life Sciences; Caregivers; CD28 antigen; CD3 antigen; Cell death; Chronic fatigue syndrome; Chronic illnesses; Cytology; Diagnosis; Disease; Economic impact; Electron microscopy; Encephalomyelitis; Evaluation; Fatigue; Fatigue Syndrome, Chronic - metabolism; Humans; Immune system; Intracellular; Leukocytes, Mononuclear - metabolism; Lipids; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Metabolism; Microscopy, Electron, Transmission; Mitochondria; Morphology; Organelles; Oxidative stress; Pathogenesis; Patients; Phenotype; Phenotypes; Pilot Projects; Platelet aggregation; Platelets; Research and Analysis Methods; Respiration; Risk factors; T cell receptors; Transmission electron microscopy; Ultrastructure; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0272703

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria. PBMCs from four participants were studied: a pair of identical twins discordant for moderate ME/CFS, as well as two age- and gender- matched unrelated subjects-one with an extremely severe form of ME/CFS and the other healthy. TEM analysis of CD3/CD28-stimulated T cells suggested a significant increase in the levels of apoptotic and necrotic cell death in T cells from ME/CFS patients (over 2-fold). Stimulated Tcells of ME/CFS patients also had higher numbers of swollen mitochondria. We also found a large increase in intracellular giant lipid droplet-like organelles in the stimulated PBMCs from the extremely severe ME/CFS patient potentially indicative of a lipid storage disorder. Lastly, we observed a slight increase in platelet aggregation in stimulated cells, suggestive of a possible role of platelet activity in ME/CFS pathophysiology and disease severity. These results indicate extensive morphological alterations in the cellular and mitochondrial phenotypes of ME/CFS patients' immune cells and suggest new insights into ME/CFS biology.