The inflammation associated with rheumatoid arthritis primarily attacks the lining of the joints (the synovium). If it persists, cartilage and bone erosion can occur and the joint becomes deformed and immobile. The muscles, tendons and ligaments surrounding affected joints can also weaken, which worsens the overall effects. The reason for the immune system reacting in this way is not yet fully understood. As is the case with other autoimmune diseases it’s very likely due a combination of genetic and environmental factors.
Inflammation is normally a sign that the body’s protective mechanisms are at work in response to infection: nearby blood capillaries swell, and fluid and immune cells move into damaged tissue to contain any infection present. However, in autoimmune conditions like rheumatoid arthritis, immune cells begin to attack the synovial membrane lining the joints; leading to unwanted inflammation and damage. The onset of rheumatoid arthritis is usually in middle life (between ages 25 and 45), although it can also affect young children (juvenile idiopathic rheumatoid arthritis).
Most people with rheumatoid arthritis have the potential to continue leading active lives, provided they receive appropriate treatment. There is currently no cure for rheumatoid arthritis, although symptoms can be readily treated and disease progression significantly slowed in most cases. Early diagnosis and management are vital in order to preserve joint movement and minimise pain and long-term disability.
About rheumatoid arthritis
Our research into rheumatoid arthritis & psoriatic arthritis
Rheumatoid arthritis and psoriatic arthritis are chronic, lifelong diseases. Current treatments, which suppress the immune system non-specifically, improve symptoms but have variable success and create long-term side effects. They often fail to prevent unpredictable, debilitating rheumatoid arthritis and psoriatic arthritis disease flares. Every flare causes measurable, irreversible joint damage and increased risk of cardiovascular disease.
Recent technological advances now allow the study of genes and proteins from thousands of individual cells within blood and inflamed joints. These single-cell sequencing technologies, alongside genome sequencing and high-dimension flow cytometry, provide unprecedented resolution to identify ‘rogue’ immune cells causing joint inflammation in arthritis.
You can help us find better treatments for rheumatoid arthritis and psoriatic arthritis by supporting our research.
Key areas of investigation
The below studies of rheumatoid arthritis and psoriatic arthritis are led by Dr Etienne Masle-Farquhar (Garvan), in close collaboration with Dr Mandeep Singh (New York Genome Centre) and rheumatologists including Dr Laila Girgis (Head of Rheumatology, St Vincent’s Hospital) and Dr. Mihir Wechalekar (Head of the Synovial Tissue Biobank, Flinders University).
These studies are supported by the Exceptional Responders in Autoimmune/Inflammatory Diseases (ERAD) Program, the HOPE Research Project, Associate Professor Owen Siggs and Professor Chris Goodnow.
Studying immune cells during rheumatoid arthitis & psoriatic arthritis disease flares.
Rheumatoid arthritis and psoriatic arthritis disease flares are unpredictable, debilitating and of unknown causes. To tackle these critical problems, Dr Etienne Masle-Farquhar and Dr Mandeep Singh are using cutting-edge single-cell sequencing methods to study immune dysregulation during flares, in close collaboration with a growing network of NSW rheumatologists, including Dr Laila Girgis, Dr Terry Kwong, Dr Ross Penglase, Dr Ric Day.
During flares, synovial fluid can accumulate excessively around joints. This excess fluid can be aspirated to reduce inflammation and pain, and rather than being discarded is now being utilized as a precious scientific resource. Within hours of a patient’s visit to hospital, aspirated synovial fluid is processed for experiments at the Garvan, by members of the Genomic Medicine and Immunogenomics laboratories.
Studying Rogue cells within affected joints.
How immune cells cause joint damage in rheumatoid arthritis remains unknown, and choosing optimal treatments to prevent this is difficult. To address this, Dr Mandeep Singh and Dr Etienne Masle-Farquhar are collaborating with Dr Mihir Wechalekar, to study immune cells within the affected joint tissue of individuals with rheumatoid arthritis, before and over the course of their treatments.
Studying underlying genetic mechanisms of arthritis.
There is a striking genetic association between rheumatoid arthritis and the rare cancer of CD8 T cells called T cell large granular lymphocytic leukemia (TLGL). TLGL cells often acquire genetic changes (mutations) in the gene STAT3. Relative to the general population, individuals with TLGL with STAT3 mutations are up to 40 times more likely to develop rheumatoid arthritis. In investigating why, Dr Etienne Masle-Farquhar and Professor Chris Goodnow demonstrated that CD8 T cells with acquired STAT3 mutations proliferate excessively, increase expression of cytotoxic molecules and cause autoimmune pathology.
The team had previously shown that acquired mutations can cause B cell-mediated autoimmune disease in Sjögren’s Syndrome. They are now investigating acquired genetic mutations in immune cells, as a possible root cause for rheumatoid and psoriatic arthritis.
National and International Collaborations
- Exceptional Responders Program, Sydney, Australia.
- St Vincent’s Hospital, Sydney, Australia.
- Royal Prince Alfred Hospital, Sydney, Australia.
- Westmead Hospital, Sydney, Australia.
- Flinders University, Adelaide, Australia.
- The Bill and Patricia Ritchie Foundation, Sydney, Australia.
- University of Queensland, Brisbane, Australia.
- Helsinki University Hospital, Helsinki, Finland.
- New York Genome Centre, New York, USA.
Our team
Etienne Farquhar
Senior Research OfficerView ProfileManu Singh
View ProfileDr Clara Young
View ProfileDr Katherine Jackson
View ProfileCaitlin Bartie
View Profile
Support our research
Your donation helps our researchers discover scientific breakthroughs that will prevent, diagnose and cure disease.Donate now