School of Infection & Immunity

Research by School of Infection & Immunity scientists has pinpointed key cells that could be targeted to prevent painful rheumatoid arthritis flare-ups.

Published in the journal Immunity, these important new findings 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 Sii researchers 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.

The 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.

In doing so, they 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 one per cent 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. For some, their arthritis settles even after treatment ends; however, 50 per cent 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.

Sii researchers hope their findings can pave the way to find new treatments that target dendritic cells in the blood before flare-ups occur, allowing more people with rheumatoid arthritis to remain in remission.

Senior author Mariola Kurowska-Stolarska, Professor of Immune Pathology and Homeostasis at Sii, 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 and who is also an Honorary Professor at Sii, added: “We hope this research is the first step to find new ways to help more arthritis patients and to optimise 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.”

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Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis

• Immunity, Volume 57, Issue 12, 2843 - 2862.e12
• Lucy MacDonald, Aziza Elmesmari, Domenico Somma, Jack Frew, Clara Di Mario, Roopa Madhu, Audrey Paoletti, Theodoros Simakou, Olympia M. Hardy, Barbara Tolusso, Denise Campobasso, Simone Perniola, Marco Gessi, Maria Rita Gigante, Luca Petricca, Dario Bruno, Lavinia Agra Coletto, Roberta Benvenuto, John D. Isaacs, Andrew Filby, David McDonald, Jasmine P.X. Sim, Nigel Jamieson, Kevin Wei, Maria Antonietta D’Agostino, Neal L. Millar, Simon Milling, Charles McSharry, Elisa Gremese, Karen Affleck, Kenneth F. Baker, Iain B. McInnes, Thomas D. Otto, Ilya Korsunsky, Stefano Alivernini, Mariola Kurowska-Stolarska.
• This research was funded by Versus Arthritis, the Wellcome Trust, and the Italian Ministry of Health.

First published: 8 January 2025