New research by University of Glasgow scientists has pinpointed key cells that could be targeted to prevent painful rheumatoid arthritis flare-ups, offering potential new hope to millions of people with the condition world-wide.
The important new findings are published in the journal Immunity and highlight the potential to use dendritic cells as early markers to predict a rheumatoid arthritis flare-up, hopefully paving the way for more patients to achieve sustained remission.
The study was led by researchers at the University of Glasgow as part of RACE (Research into Inflammatory Arthritis Centre ‘Versus Arthritis’ a collaboration between the Universities of Glasgow, Newcastle, Birmingham, and Oxford) along with Universitario A. Gemelli IRCCS in Rome.
To carry out the study, the research team examined the joints of rheumatoid arthritis patients by analysing their tissue using a novel technique called spatial transcriptomics, which allows for the precise identification of individual cell locations.
The researchers discovered a crucial difference in the behaviour of dendritic cells, between people who are likely to experience flare-ups and those who are not. In particular, in patients at risk of flare-ups, dendritic cells were detected in the blood weeks before the recurrence of the disease, suggesting these cells could be used as biomarkers – or potential treatment targets – to help keep people in remission.
The latest figures show that around 450,000 adults in the UK have rheumatoid arthritis, while around 1% of the world’s population are affected. A painful and sometimes debilitating condition, rheumatoid arthritis commonly starts in adults between the ages of 40 and 60 years-old, and is more common in women than men.
Although treatments have improved, many people experience painful and unpredictable flare-ups. While for some patients, their arthritis settles even after treatment ends, 50% of patients experience a flare-up within weeks or months after stopping treatment.
Dendritic cells are often described as ‘cell detectives’, or information gatherers, because of their role capturing and processing information from other cells in the body. These key cells are responsible for gathering clues about potential threats and then either activating or suppressing other immune cells, known as T-cells.
In patients in remission, without any flare-ups, dendritic cells do the job of suppressing T-cells. By contrast, in active arthritis dendritic appear to cells migrate from the blood to the joints, causing inflammation and joint damage by instructing T-cells to attack.
The researchers hope their findings can pave the way to find new treatments that target dendritic cells in the blook before flare-ups occur, allowing more people with rheumatoid arthritis to remain in remission.
Professor Mariola Kurowska-Stolarska, senior author of the study from the University of Glasgow, said:
“Recent advancements in technology allow us to examine tissue at high resolution, identifying specific cell-to-cell interactions that cause pathology. This helps to pinpoint the cause of diseases, such as flare-ups, before they begin.
Professor Stefano Alivernini, senior co-author of the study from the Fondazione Policlinico Gemelli IRCCS and Università Cattolica del Sacro Cuore from Rome, said:
“We hope this research is the first step to find new ways to help more arthritis patients and to optimize their management, letting them stay symptom free and remain in remission after their therapeutic journey.”
Dr Caroline Aylott, Head of Research Delivery at Versus Arthritis, said:
“Flare-ups are a painful and frequent challenge for those living with rheumatoid arthritis, often with debilitating effects that disrupt daily life.
“By using this new technology, researchers are able to look in more detail than ever before at the cells responsible for inflammation in the joint. This means we are closer to using these as markers to predict when painful flare-ups will occur, which will help people to manage their rheumatoid arthritis better.
“This new research, funded by Versus Arthritis along with grants from the Wellcome Trust and the Italian Ministry of Health, represents a promising step towards achieving sustained remission and improving quality of life for people with arthritis. By supporting ground-breaking studies like this, we are advancing towards a future where arthritis is preventable, manageable, and treatable.”
The study, ‘Distinct Tissue-Niche Localization and Function of Synovial Tissue Myeloid DC Subsets in Health, and in Active and Remission Rheumatoid Arthritis’ is published in Immunity. The work was funded by Versus Arthritis, the Wellcome Trust and Italian Ministry of Health.