UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis

Wilkinson, Meredyth Grace Llewellyn; (2018) Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of M.Wilkinson e-thesis .pdf]
Preview
Text
M.Wilkinson e-thesis .pdf - Accepted Version

Download (11MB) | Preview

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.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10048930
Downloads since deposit
136Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item