A team of Irish scientists has pinpointed two potential avenues for developing treatments of rheumatoid arthritis – a painful inflammatory disease affecting an estimated 350 million people worldwide.
Led by Dr Achilleas Floudas and Prof Ursula Fearon from Trinity College Dublin's Molecular Rheumatology group, the team discovered "a new cell population that is especially troublesome in people living with the disease, and also learned how these cells accumulate in the joints".
Rheumatoid arthritis is the most common form of inflammatory arthritis, affecting 1 to 2 per cent of Irish people. It is characterised by progressive joint inflammation, damage and disability, which severely impacts a patient’s quality of life.
There is currently no cure and, contrary to popular belief, it is not a disease of older people. Disease onset occurs in adults between 35 to 45 years of age, and it also afflicts children.
"B cells" are key cells of the immune system, which are responsible for the production of antibodies that fight infections. However, with rheumatoid arthritis, these B cells – for reasons not yet fully understood – fail to recognise friend from foe and thus attack the joints, Dr Floudas explained. This leads to the tell-tale joint inflammation that causes such pain in patients.
Their work puts two potential new therapeutic targets for the disease on the radar, Dr Floudas added. The research has been published in the journal JCI Insight.
“We discovered a novel population of B cells in the joints of patients with rheumatoid arthritis, and these cells are more inflammatory and invasive than those we knew before,” he said.
Their damaging effects rely on production of specific coded messages, in the form of proteins called cytokines, and energy pathways within the cells which essentially maintain their activation. Basically, they “switch on”, cause inflammation, and are maintained within the environment of the inflamed joint.
“We also discovered a new mechanism by which these B cells accumulate in the joint, by pinpointing the protein that seems to be responsible for attracting them to the joints,” he said.
They were some way away from a therapeutic solution but if they could find a way of targeting these B cells and/or the protein that attracts them to the joints, “we can one day hope to develop a therapy that could impact positively on millions of people.”
Prof Douglas Veale from St Vincent's University Hospital, Dublin, along with specialists in TCD's School of Engineering, Centre for Biomedical Engineering, and School of Biochemistry and Immunology contributed to the research. Other collaborators included researchers and clinicians from St Vincent's; UCD; Tallaght University Hospital and Janssen Research & Development in Pennsylvania. The research was funded by the HRB and Arthritis Ireland.
Meanwhile Dr Paulina Szklanna has won the 2020 UCD AbbVie Innovation Award for the potential within her research to develop an affordable clinical tool based on blood-borne biomarkers to track progression of multiple sclerosis over time.
MS is an inflammatory and neurodegenerative condition that is the most common cause of non-traumatic disability in young adults. Some 9,000 Irish people are currently living with MS and their individual disease progression is highly variable. Clinically predicting the course of the disease remains a huge challenge and biomarkers are urgently required to help in this effort.
