Mensah, Fane Kojo Fosu;
(2019)
Investigations of B cell phenotype and metabolic function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition characterized by multiple systemic symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Immune system dysfunction triggered by infection or other insult is generally assumed to be a major causal factor that contributes to changes in energy metabolism leading to the pathophysiology of ME/CFS. B cells became of interest after reported clinical improvement following B cell depletion-therapy with rituximab (anti-CD20). A possible but undefined role for B cells was, therefore, proposed. The initial aim of this thesis was to explore subtle alterations in B cell subsets in ME/CFS patients which could be used as a diagnostic and prognostic marker for the disease. Further, the dynamic nature of B cells was utilised as a model to observe changes in energy demand and for performing comprehensive metabolomic profiling of activated and maturating B cells under culture conditions. Results for HC and ME/CFS patients could, therefore, be compared under similar conditions of stress. Flow-cytometric analysis of CD19+B cells revealed increased frequencies and expression of the heat-stable antigen CD24 in ME/CFS patients, as well as an increased memory B cell subset (CD21+CD38-). Retention of CD24 was linked to unresponsiveness to proliferative and pro-apoptotic signals and phosphorylation of AMPK (pAMPK). PAMPK was found to be largely confined to IgD+IgM+ memory B cells. Metabolic analysis of cell culture supernatant using 1H-NMR spectroscopy revealed significant correlations between CD24+B cell frequencies and the usage of glucose and the production of lactate. Novel findings described in this thesis, therefore, established a link between CD24 positivity of B cells and energy metabolism. Immunophenotype and metabolite profiles of cultured B cells from HC and ME/CFS patients were also revealed to respond with different dynamics to interventions, thereby providing a potential platform for more focused research and diagnosis.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigations of B cell phenotype and metabolic function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080812 |
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