Please use this identifier to cite or link to this item: http://theses.ncl.ac.uk/jspui/handle/10443/1773
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dc.contributor.authorLocke, James-
dc.date.accessioned2013-08-02T08:53:14Z-
dc.date.available2013-08-02T08:53:14Z-
dc.date.issued2012-
dc.identifier.urihttp://hdl.handle.net/10443/1773-
dc.descriptionPhD Thesisen_US
dc.description.abstractRheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation at multiple joints. Because of the association of the condition with certain alleles of the DRB1 gene which encodes the β-chains of human leukocyte antigen (HLA)-DR molecules, it has been postulated that auto-reactive CD4+ T-cells - specific for joint-associated autoantigens presented in the context of these RA-associated HLA-DR molecules – are involved in the initiation or perpetuation of the disease process. In addition, citrullination of autoantigen-derived peptides may enhance their binding affinity to RA-associated HLA-DR molecules, implicating citrullinated autoantigens in RA pathogenesis. Since RA primarily affects the joints, proteins of articular origin and those expressed in the joints such as human cartilage glycoprotein 39 (HCgp39), type II collagen (CII), aggrecan, α-enolase, fibrinogen and vimentin are candidate autoantigens in RA. However, it has been difficult to consistently detect T-cell responses to these candidate RA autoantigens in RA patients. In this project, I hypothesised that T-cell responses to candidate autoantigens are heightened in RA patients compared to healthy subjects and that the T-cell responses of RA patients are pro-inflammatory while those of healthy subjects are not. I first optimised an experimental system for detecting autoantigen-specific T-cell responses and applied the protocol to measure proliferative and cytokine production responses of peripheral blood mononuclear cells (PBMC) from RA patients, healthy subjects and disease controls to unmodified and citrullinated whole protein and peptide forms of the candidate RA autoantigens mentioned above. Responses to the candidate autoantigens were readily detectable in RA patients, healthy subjects and disease controls. Furthermore, I found no evidence of increased immunogenicity of citrullinated peptides versus their unmodified counterparts. Thus the study failed to provide evidence that T-cell responses to either unmodified or citrullinated autoantigens are important in RA pathogenesis.en_US
dc.description.sponsorshipArthritis Research UK:en_US
dc.language.isoenen_US
dc.publisherNewcastle Universityen_US
dc.titleThe role of joint-associated autoantigen-specific immune responses in rheumatoid arthritisen_US
dc.typeThesisen_US
Appears in Collections:Institute of Cellular Medicine

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