To identify molecular signatures that can predict disease onset in 'at-risk ACPA+' individuals and disease progression in RA patients

Inflammation is a critical process in fighting infection. However, if uncontrolled, it can contribute to the development of autoimmune disease, including inflammatory forms of arthritis such as rheumatoid arthritis (RA), which causes joint destruction and disability. Targeted therapies have advanced the treatment of RA, however a significant proportion of patients have sub-optimal responses, no response and suffer adverse events.

Currently, it is impossible to predict;

  1. who will develop RA,
  2. once diagnosed which patients will develop more severe and erosive disease, and
  3. which patients will respond to a specific treatment at time of onset.

These drugs are very expensive, therefore a 'trial and error' approach is not a cost-effective strategy, increasing strain on an already overstretched health budget. Thus, there is a major need for smart and safe use of effective drugs for treatment of RA.

Recent research has started to focus on subjects 'at-risk' of arthritis or 'pre-RA'. These subjects have no clinical signs of inflammation, however they have increased levels of circulating autoantibodies, with a significant percentage of these subjects progressing to RA.

In this collaborative project involving basic scientists, clinicians and patients, we will:

  1. identify the mechanisms that drive inflammation in immune cells pre disease onset,
  2. elucidate how these cells utilize energy in order to maintain their activated inflammatory phenotype, and
  3. test if activation or inhibition of these mechanisms promotes resolution of inflammation in synovial tissue cells.

This approach will assist in the identification of new disease markers and drug candidates for the treatment of patients at different stages of RA progression and possibly other autoimmune diseases.

Award Date
27 June 2019
Award Value
Principal Investigator
Professor Ursula Fearon
Host Institution
Trinity College Dublin
Investigator Led Projects