Researchers from Cardiff University in Wales think they have discovered something with the potential to prevent the onset of an aggressive form of rheumatoid arthritis (RA) that is especially hard to treat. The team is now shedding light on how interleukin-27, an immune system protein, regulates the inflammatory process in lymphoid-rich RA. The researchers indicate that they are the first to be able to explain how this variant of the disease develops.
Understanding this process, they said in the October 6, 2015 news release, will enable doctors to divide patients into different sub-groups based on the often greatly varying patterns of disease, which is influenced by how much interleukin-27 is present in each patient’s joints.
The researchers also anticipate that their identification of interleukin-27 involvement in this specific disease context will kick-start the search for new drugs that manipulate the pathways controlled by this factor. Dr. Gareth Jones, from Cardiff University School of Medicine’s Institute of Infection & Immunity, said in the news release, “…The key is identifying which drug is best suited for an individual patient. Making the correct treatment decisions, sufficiently early in the disease process will improve disease outcome, enhance a patients wellbeing and overall quality of life.”
Dr. Jones told OTW, “The objective of our research is to understand the immune mechanisms responsible for driving tissue damage, chronic disease progression and autoimmunity. The clinical features of joint inflammation vary considerably from one rheumatoid arthritis patient to the next. We are interested in determining the inflammatory processes that account for this diversity. Our study focused on a particular subtype of rheumatoid arthritis pathology, called the ‘follicular pathotype, ’ that is associated with severe disease symptoms and a poor response to some of the mainstream therapies (e.g. anti-TNF). This type of synovial pathology (affecting 30-40% of patients) is characterised by the presence of highly organised clusters of activated immune cells, called ectopic lymphoid-like structures (ELS), which are dotted throughout the inflamed joint tissue and contribute to local pathology. Using cell-based systems, experimental models of arthritis and ultrasound-guided synovial biopsies from rheumatoid patients with early disease, we show that the cytokine interlukin-27 interferes with the development of follicular-type pathology in rheumatoid arthritis.
“Using experimental models of inflammatory arthritis we describe a molecular mechanism to explain how synovial ELS develop, which may aid the design of more targeted therapies for future patient treatment. Based on our analysis of joint tissues from rheumatoid patients, it is anticipated that the detection of interleukin-27 in the joints may also be used as a predictive marker for diagnostic purposes and decision-making regard the best course of therapy for patients with ELS-associated disease.”
“Our data suggest that the ability of IL-27 to dampen T helper cell responses, specifically Th17 cells, accounts for its suppressive role in synovial ELS formation. This is the first study describing IL-27 as a regulator of ELS development in chronic inflammatory diseases. Our data, together with previously described anti-inflammatory roles for IL-27 in chronic inflammatory conditions, highlight its potential as a therapeutic.
