Altered immune metabolism in myalgic encephalomelitis/chronic fatigue syndrome
Mandarano, Alexandra Hope
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-systemic disease that is debilitating to patients. The cause of ME/CFS is unknown and there are no approved diagnostic tests or treatments. The onset of the disease often resembles a flu, and ME/CFS involves immune related symptoms. Patients suffer from severe fatigue and post-exertional malaise, suggesting potential dysfunction in energy metabolism. ME/CFS research has revealed evidence of immune dysfunction. Furthermore, there is increasing evidence of metabolic disturbances in ME/CFS patients. However, relatively little is known about metabolism within patient immune cells. Immune cells require specific metabolic programs to maintain quiescence, as well as to respond to an immune challenge. Immune cells must reprogram their metabolism to induce particular metabolic pathways following activation. Effector cells rely on metabolism for proliferation, differentiation and specific effector functions. Aberrant immune cell metabolism is a feature of numerous human diseases and can be a consequence of both infection and autoimmunity. To determine whether immune metabolism is altered in ME/CFS, I sought to characterize metabolism in specific immune cells. To this end, I characterized metabolism in total peripheral blood mononuclear cells (PBMCs), as well as isolated T, B and NK cells from healthy control and ME/CFS subjects. I used Seahorse Extracellular Flux analysis to assay mitochondrial and glycolytic metabolism in these cells. Additionally, I investigated the capacity of ME/CFS immune cells to reprogram their metabolism by characterizing metabolism after activation. I then examined mitochondria and markers related to activation and metabolism on ME/CFS and healthy control lymphocytes. Finally, I analyzed this data for correlations with plasma cytokine abundance, metadata and the frequency of immune cell subpopulations. My results indicate that cellular metabolism is uniquely altered in specific ME/CFS lymphocytes. These findings are consistent with a potential infection in ME/CFS and likely have functional consequences for the patient immune system.
Immunology; Cellular biology; Biochemistry; chronic fatigue syndrome; immune; myalgic encephalomyelitis; Glycolysis; Mitochondria; Metabolism
Hanson, Maureen R.
Gu, Zhenglong; Chang, Pamela V
Genetics, Genomics and Development
Ph.D., Genetics, Genomics and Development
Doctor of Philosophy
dissertation or thesis