Ongoing examination of the PD-1:PD-L1 pathway throughout the evolution of Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic autoimmune disease which causes joint destruction, disability, and increased mortality. While treatment has improved, only 1:4 patients achieve full remission and predicting who will develop severe disease or who will respond to treatment is difficult. This research will examine an immune pathway known as PD-1 and aims to understand how this pathway may contribute to the development of RA. PD-1 is a molecule on the surface of immune cells such as T cells and Dendritic Cells. It is known as a "negative regulator" meaning, when it is activated or "switched on" it dampens down the immune response - in this way it can be viewed as a "brake" in slowing down inflammation in the body. We have previously demonstrated that this molecule is found at a high level in the joints of RA patients, even patients who are in early stages of disease. Therefore this proposal will aim to understand why this "brake" is present at high levels in the joints of RA patients, and assess if it has an alternative function in these patients, which may in fact be contributing to their disease. This approach will aim to identify new candidate treatments, enable clinicians to stratify or group patients, thus facilitating early and more personalised treatment interventions. Ultimately this will allow patients to be treated with the right medication, at the right time before their disease becomes severe.

Award Date

30 June 2022

Award Value

€769,054

Principal Investigator

Dr Mary Canavan

Host Institution

Trinity College Dublin

Scheme

Emerging Investigator Awards 2022