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

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. 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.

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

“…Moreover, both IL22 and IL10 protect gut mucosal immunity and act on the same receptors, loss of these cytokines may trigger the pathogenesis of long COVID and ME/CFS [301,302]. These findings are in line not only with our earlier hypothesis but also with the results novel studies that have connected dysfunctional efferocytosis with fatiguing illnesses, including FM, ME/CFS, and GWIs [303][304][305].…”

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses

“…CD41a is a component of GPIIb/IIIa complex – the platelet receptor that binds fibrinogen and von Willebrand factor, and mediates platelet adhesion and aggregation, and clotting. Further indications of platelet hyperactivity come from a recent study using transmission electron microscopy, where significant platelet spreading and aggregation was documented in ME/CFS samples [ 172 ]. In contrast, a study from 2006 found neither platelet hyperactivation nor hypercoagulation in their ME/CFS cohort [ 173 ].…”

“…It is plausible to hypothesize that viruses (and potentially other microbes) are contributing to the clotting pathology observed in ME/CFS individuals [ 42 , 43 , [170] , [171] , [172] ]. Herpes viruses, the virus types most implicated in ME/CFS, are known to influence coagulation in a prothrombotic manner [ [308] , [309] , [310] ].…”

Oxidative Stress is a shared characteristic of ME/CFS and Long COVID

“…In addition to its central role in generating over 95% of a cell's energy through ATP, changes in mitochondrial morphology and function accompany lymphocyte differentiation and activation 21 , with mitochondria driving cytokine production 22 , thereby linking energy metabolic deficits in immune cells with chronic inflammation. Along these lines, studies have hypothesized and identified signatures of mitochondrial dysfunction among CFS and LC patients, including down-regulation of host mitochondrial genes even after COVID-19 recovery 23 , altered mitochondrial morphology 24 in ME/CFS donor T cells, decreases in mitochondrial membrane potential 25 among recovered COVID-19 subjects' lymphocytes, and redox dysregulation in both ME/CFS and COVID-19 26 .…”