Study offers potential for early diagnosis and therapeutic intervention for rheumatoid arthritis

There is currently no cure for rheumatoid arthritis (RA), which affects 40,000 people in Ireland. The disease costs approximately $22,000 per patient per year, with an overall cost to the healthcare system of approximately $608 million. Only 1 in 4 patients achieve remission and a significant proportion of patients have suboptimal responses or no response to currently available therapies.

As it is impossible to predict who will develop severe, erosive disease and who will respond to treatment, a trial and error approach prevails, leading to potentially irreversible joint damage before the patient has received appropriate treatment.

Now, a study led by researchers from Trinity College Dublin and St Vincent’s University Hospital offers a better understanding of the site of inflammation in RA, which will enable the development of new treatment strategies or predictive biomarkers that could support the potential of a personalized medical approach. The study is published in the journal Scientific advances.

This work was led by Professor Ursula Fearon and Dr Megan Hanlon from Trinity’s Molecular Rheumatology Group, as well as Professor Douglas Veale from St Vincent’s University Hospital.

The team conducted an in-depth investigation of a specific population of cells: macrophages that reside in the synovium of RA patients, individuals at risk for RA, and healthy controls. Researchers demonstrated, for the first time, the presence of a dominant macrophage subtype (CD206+CD163+ expressing CD40) in the inflamed synovium of RA, which was significantly associated with disease activity and to response to treatment.

The team identified that these cells reside in the joint. In health they play a protective role, but in disease, for reasons we are not sure of, they become pro-inflammatory and release proteins called cytokines which induce inflammation and have the ability to activate the type of invasive fibroblastic cells, which leads to cartilage. and bone destruction.

Researchers identified that the pro-inflammatory status of these macrophages is maintained by specific signaling and metabolic pathways within the joint, targeting of which can induce resolution of inflammation. Importantly, the team identified that these changes in macrophage status occurred before disease onset.

Combined, these findings identify the presence of an early pathogenic macrophage cell/gene signature that shapes the inflammatory environment of the RA joint and represents a unique opportunity for early diagnosis and therapeutic intervention.