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Characterisation of cytokine expression in early synovitis and established rheumatoid arthritis

Yeo, Lorraine (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

In rheumatoid arthritis (RA), chronic inflammation and destruction of the joint is driven by local production of cytokines. My aims were to characterise cytokine mRNA expression in multiple synovial fluid cell populations in early and established RA and to study these, in addition to whole synovial tissue, in early synovitis patients in relation to disease outcome.
I established a novel method to determine cytokine mRNA expression in synovial fluid CD4 T cells, CD8 T cells, B cells, macrophages and neutrophils directly ex vivo. I made several novel observations, for example RA synovial fluid B cells expressed high levels of RANKL. As RANKL drives bone resorption, this suggests a potential role for B cells in bone erosion in RA. RANKL protein was expressed by B cells in synovial tissue, and mainly by memory B cells in synovial fluid. Furthermore, synovial RANKL levels were reduced after treatment with the B cell depleting therapy, rituximab.
Overall, both in whole synovial tissue and in sorted cells, the cytokine mRNA expression profile was very similar in early synovitis patients who subsequently developed RA or had resolving synovitis, and in patients with early or established RA. In comparison, cytokines and chemokines were upregulated in early and established arthritis patients compared to uninflamed controls. The finding that cytokine mRNA expression is largely similar in early synovitis patients who develop RA or have resolving disease, and in the early and established phases of RA, suggests that cytokine expression is reflective of general synovial inflammation, rather than being specific for early synovitis outcome or stage of RA.

Type of Work:Ph.D. thesis.
Supervisor(s):Scheel-Toellner, Dagmar and Raza, Karim
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QP Physiology
QR180 Immunology
RC Internal medicine
Institution:University of Birmingham
ID Code:3340
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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