Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747713
Title: Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis
Author: Wilkinson, Meredyth Grace Llewellyn
ISNI:       0000 0004 7232 2826
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Abstract:
The Inflammatory Idiopathic Myopathies (IIM) are a rare group of myopathic autoimmune diseases diagnosed in both adults and children. Patients present with proximal muscle weakness and Gottron’s papules. Immunohistochemical analysis of muscle tissue from these patients has identified immune cell infiltrate and the expression of pro-inflammatory cytokines however, little is known about the peripheral immunological profile in juvenile and adult patient groups. There are three aims: Firstly, to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in the blood of Juvenile Dermatomyositis (JDM) patients. Secondly, to identify specific immune cell signatures and cytokine profiles for myositis disease subtypes and correlate this data with measurements of disease activity. Finally, to delineate a correlation between the up-regulated type I interferon signature and dysfunction of cholesterol homeostasis in immune cells. Using a combination of cell culture, flow cytometry, RNA-seq, q-PCR and ELISA techniques this study has assessed the immune cell signature, B cell biology and IFN related mechanisms in patients with IIM. The results identified that JDM patients with active disease have a significantly expanded immature B cell population which was correlated with a type I IFN signature. Activation through TLR7 and IFN- may drive the expansion of immature B cells in JDM and skew the cells towards a more pro-inflammatory phenotype. There are unique immune signatures in adult disease sub-types, one example was an expanded Th17 population seen in adult dermatomyositis (ADM). Lastly, IFN- stimulation of T and B cells does change the expression of some genes that are part of the Hallmark cholesterol homeostasis pathway. In conclusion, the work undertaken during my thesis provides further evidence that anti- IFN biologics could be efficacious in the treatment of JDM. Also, the need for further investigation for the use of IL-17A inhibitors in the treatment of IIM.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.747713  DOI: Not available
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