Stromal cell subtypes define distinct pathogenesis in RA and PsA

Arthritis is a leading cause of disability affecting up to 15% of the Irish population. 2% suffer from inflammatory arthritis (IA) such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The cost of treating patients with IA in Ireland is ~€20,000/patient/year.

Activation of our immune cells is a key mechanism by which our body fights infection. However, if uncontrolled, immune-cells don’t switch off and contribute to development of autoimmune-diseases (RA and PsA), leading to inflammation and subsequent joint damage and disability. In the case of PsA there is also associated skin psoriasis. In RA and PsA immune-cells in our blood become activated and travel to the joint where they release pro-inflammatory mediators that activate a specific cell-type in the joint called the ‘synovial-fibroblasts’ which significantly contributes to cartilage and bone damage, leading to functional disability. Targeted medicines against proinflammatory mediators and/or cells at the site of inflammation has advanced RA/PsA treatment, however a significant proportion of patients partially respond, have no response or experience side-effects. While common pathogenic features exist between RA and PsA, there are also significant differences which may explain their distinct clinical features, and more importantly, may explain different responses to specific therapies that impact on disease outcomes. Currently, we cannot predict which patients will develop more severe/erosive disease, who will respond, and why RA and PsA have common and distinct responses to current therapies. Thus, the current project focuses on isolating cells from the site of inflammation in the joint ‘the synovium’, and (i) identifying how these cells differ in their activation state between RA and PsA, (ii) how these differences contribute to cartilage and bone damage, and (iii) can this impact on disease progression and response. This approach will allow identification of new disease markers/drug-candidates for the treatment of RA, PsA and possibly other autoimmune-diseases.
 

Award Date
01 July 2022
Award Value
€358,470.00
Principal Investigator
Professor Ursula Fearon
Host Institution
Trinity College Dublin
Scheme
ILP