Research findings offer a unique opportunity for early diagnosis and therapeutic intervention for rheumatoid arthritis
Published study proposes a better understanding of the site of inflammation in the disease
Currently there are no cures for rheumatoid arthritis (RA) which affects 40,000 people in Ireland. The disease costs an estimated €20,000 per patient, per year with an overall cost to the health system of ~€544 million. Only 1 in 4 patients achieve remission and a significant proportion of patients have suboptimal responses or no response at all to current 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 potential irreversible joint damage before the patient has received the correct treatment.
Now, a study published this morning [Thursday 26 th September 2024] by researchers in Trinity College Dublin and St Vincent’s University Hospital proposes a better understanding of the site of inflammation in RA which will allow for the development of new treatment strategies or predictive biomarkers which could support the potential for a ‘personalised medicine’ approach. The study is published in the journal Science Advances.
This work was led by Professor Ursula Fearon and Dr Megan Hanlon from the Molecular Rheumatology Group in Trinity, and by Professor Douglas Veale, from St Vincent’s University Hospital.
The team performed an in-depth investigation of a specific population of cells: ‘the macrophages’ that reside in the synovium of RA patients, ‘individuals-at-risk’ of RA and healthy controls. Researchers demonstrated for the first time, the presence of a dominant macrophage subtype (CD40-expressing CD206+CD163+) in the inflamed RA synovium, which importantly was associated with disease-activity and treatment response.
The team identified that these cells are resident in the joint which, in health play a protective role, but in disease - for reasons we are unsure of - become pro-inflammatory, and release proteins called cytokines that induce inflammation, and also have the ability to activate the invasive fibroblast cell type which leads to cartilage and bone destruction.
Researchers identified that the pro-inflammatory status of these macrophages is maintained by specific signalling and metabolic pathways within the joint, the targeting of which may induce resolution of inflammation. Importantly the team identified that these changes in the macrophage status occurred pre-disease onset.
Combined, these findings identify the presence of an early pathogenic macrophage cell/gene signature that shapes the RA joint inflammatory environment and represents a unique opportunity for early diagnosis and therapeutic intervention.
KEY FINDINGS
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Ursula Fearon, Professor of Molecular Rheumatology, School of Medicine, Trinity College Dublin said:
“ This is an important breakthrough in our understanding of what goes wrong at the initial stages of disease in RA, which also has an impact on patient’s progression and relapse. We have identified a dominant macrophage subtype/gene signature associated with driving the pro-inflammatory responses early in disease and therefore reprogramming of macrophages towards resolution of inflammation has the potential to be therapeutically targeted.”
Dr Megan Hanlon, post-doctoral fellow in Molecular Rheumatology, School of Medicine (at the time of the study, and now based in Harvard University), said:
“ The presence of these macrophages in individuals at risk of developing RA, highlights the possibility of an early cellular biomarker of disease onset, resulting in early treatment intervention.”
READ: you can read the paper: Loss of synovial tissue macrophage homeostasis precedes rheumatoid arthritis clinical onset at the following link: https://www.science.org/doi/epdf/10.1126/sciadv.adj1252
Ends
Science Advances
Meta-analysis
Human tissue samples
Loss of synovial tissue macrophage homeostasis precedes rheumatoid arthritis clinical onset
25-Sep-2024