Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/ chronic fatigue syndrome via transmission electron microscopy: A pilot study from Stanford University
Research paper conclusion:
In summary, only a handful of studies have been performed on the ultrastructural characteristics of ME/CFS muscle cells and no data are available on other cell types. Our study analyzes immune cells from ME/CFS patients for the first time and provides insights into disruption into immune cell structure and function.
Immune cell – A cell that is part of the immune system and helps the body fight infections and other diseases.
Although our sample size is small this study suggests new directions for characterization of morphological and ultrastructural dysregulation of affected tissues at single cell level. Our finding that the proportion of apoptosis and necrosis increase in stimulated T cells in patients with ME/CFS and that the rate of mitochondrial swelling correlates with disease severity is robust and supports previous research but needs well-adjusted replication.
Elevated lipid droplet and platelet hyperactivation in the extremely severely ill ME/CFS patient highlights the roles genetics and epigenetics risk factors interplay in the onset, severity, prognosis, and comorbidity. It further reveals the power of genetics testing when combined with proper functional, diagnostic and research testing in patients with chronic complex conditions.
Replicating this study with larger cohorts, more measurement time points, and perhaps a combination of other cell death assays would expand our knowledge of morphological characteristics of the immune cell in ME/CFS etiopathogenesis.
Authors:
Fereshteh Jahanbani, Rajan D Maynard, Justin Cyril Sing, Shaghayegh Jahanbani, John J Perrino, Damek V Spacek, Ronald W Davis, Michael P Snyder in PLoS One Vol 19, #8, p e0272703 August 9, 2022
Research abstract:
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.
Method:
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.
Results:
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.
Conclusion:
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.
