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Title: Functional and transcriptional characterisation of synovial fibroblasts in early inflammatory arthritis and established rheumatoid arthritis
Author: Juárez Pérez, María Jesús
ISNI:       0000 0004 5359 6020
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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A pathogenic role for synovial fibroblasts has been established based on the study of samples originating from patients with longstanding rheumatoid arthritis (RA). To assess whether these cells also have such role in early RA and whether they play a part in the resolution of inflammatory arthritis, functional and transcriptional characterisation was performed on synovial fibroblasts from patients in five distinct outcome groups: normal joints, resolving arthritis, very early RA, early RA and longstanding RA. Functional characterisation revealed differences in migration rates between groups. Migration rates of very early RA and longstanding RA synovial fibroblasts were significantly slower than those of normal ones. No differences in invasive characteristics were identified. Transcriptional analysis demonstrated differing transcriptional signatures between very early and longstanding RA synovial fibroblasts in both, unstimulated and TNF stimulated samples. No differences in the transcriptomic profile of resolving and very early RA cells were identified. The study of transcriptional responses to TNF stimulation in each outcome group revealed generic changes in response to pro-inflammatory stimuli as well as outcome group-specific responses. These data extend previous observations of the pathogenic role of synovial fibroblasts indicating that they may play a role in early RA and providing clues to potential targets differentiating early and late RA.
Supervisor: Not available Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine