Two recently published papers by researchers at Trinity College Dublin (TCD) offer fresh insight into joint inflammation in patients with rheumatoid arthritis (RA).

The Molecular Rheumatology Group at TCD’s School of Medicine is working to better understand the complex cellular and molecular events that occur directly in the affected joints of patients.

It is hoped the group’s work will identify new treatment strategies for a condition that currently affects around 1% of the world’s population and can cause severe pain, disability and mental health difficulties, such as depression.

By examining cells and tissue from the site of inflammation in well-defined patient cohorts, the group aims to understand what drives the disease and how cells interact with each other to orchestrate the inflammatory response.

Currently, two of the groups research fellows, Dr Mary Canavan and Dr Achilleas Floudas, are examining the cells in the synovium - the primary site of the inflammatory process - which if left untreated leads to irreversible damage to the adjacent cartilage and bone.

Two cell types involved in the inflammation process are dendritic cells and T cells.

Dr Canavan’s research provides unique and previously unexplored insights into the complex role dendritic cells may have in joint inflammation in patients with RA.

Dendritic cells are a key immune cell in the body and there are many different subtypes, each with its own unique role. This was the first study of its kind to examine these cells at the site of inflammation - that is, in the affected joints of the patients and not just in the peripheral blood.

“There is no doubt that the activities of these dendritic cells have consequences for neighbouring cells in the synovium, such as T cells.

“Our findings also demonstrated that this CD1c+ dendritic cell population produces large amounts of ‘matrix degrading enzymes’, which can destroy cartilage and bone. Therefore, this study provides unique and previously unexplored insights into the complex role dendritic cells may have in joint inflammation in patients suffering from RA,” Dr Canavan explained.

Her research was published in the journal, Frontiers in Immunology. 

Meanwhile, Dr Achilleas Floudas’s study examined the previously unconsidered population of immune T cells found in synovial tissue and how they become dysfunctional and exert many negative impacts associated with RA.

Crucially, these cells begin to malfunction before the clinical onset of RA. As a result, the researchers hope they may one day serve as “early-warning flares” that may allow clinicians to detect at-risk individuals and act before RA becomes established.

“The window for effective therapeutic intervention in RA is limited. Current T cell-specific therapies for treatment are broad and affect all T cells, irrespective of their contribution to disease pathogenesis and progression, therefore not differentiating between protective and pathogenic T cell responses.

“Additionally, if we can spot the early-warning flares set off by specific T cells in the synovial tissue of at-risk individuals, we should be able to extend the window for effective therapeutic intervention,” he explained.

Dr Floudas’ findings are published in the journal, Annals of Rheumatic Disease.

According to Prof Ursula Fearon, professor of molecular rheumatology at TCD, understanding the role that these specific immune cells play in driving inflammation in individual patients could lead to the development of “precision treatments that prevent onset or impact early in the disease”.

This, she added, would have a “significant impact” on the quality of life of those affected.