Possible new disease targets for children with arthritis revealed by first-of-its-kind study
Groundbreaking research by a team from BHP’s Birmingham Children’s Hospital and the University of Birmingham – working with UCL and Great Ormond Street Hospital – has revealed important clues into what is driving disease in children with arthritis.
Cutting-edge techniques have allowed scientists to uncover the unique architecture of cells and signals inside the joint as inflammation takes hold, for the first time.
Published in Science Translational Medicine, the study investigated juvenile idiopathic arthritis in children – caused by the immune system mistakenly attacking joints – which affects more than 10,000 children in the UK. It causes swelling, stiffness and pain in the joints over years or decades, leading to damage of the joints and long-term disability. While there are pain management treatments available, which in some cases achieve remission, there is no cure – and it can take time to find which treatment works for each person. Treatments don’t work in the same way for every child, suggesting there are hidden differences between individuals that we are yet to fully understand.
Deepening the scientific and clinical community’s understanding of the condition is vital if more effective treatments are to be found, and undertaking biopsies in young children provides a new way forward. The study’s potential has been advocated for by families of children with arthritis, who agreed that the procedure would be acceptable to families, especially compared to living with a chronic inflammatory disease.
In a world first, tiny tissue samples were collected from the joint lining when children were having medicine injected into the joint, which were then analysed with advanced imaging and gene-profiling technologies. The fine resolution maps of the joints revealed differences between children of different ages and cell changes in those with more severe disease – creating unique cellular ‘fingerprints’ which may help researchers understand why some drugs work better for some children, and not others. The joints of children with arthritis also looked significantly different to those with adults, demonstrating the need to understand arthritis in children better.
Professor Adam Croft, Versus Arthritis Professor of Rheumatology at the University of Birmingham and chief investigator of the study, said: “We know how frustrating it can be for families and young people to find a drug that best works for their arthritis. Finding ways to better predict which medicines will be beneficial for a particular child would mean we were able to treat the disease more rapidly and effectively. To achieve this goal, we first needed to understand what cells make-up the lining of the joint where the inflammation occurs. Equipped with that knowledge, we can now start to tackle the next challenge, determining how these cellular fingerprints within the joint tissue can help us predict which drug will work best, ensuring we give the right drug, to the right child, at the right stage of their disease.”
Professor Lucy Wedderburn, University College London Great Ormond Street Institute of Child Health and Consultant of Paediatric Rheumatology at Great Ormond Street Hospital said: “This study represents a real step change in our work with children and young people who live with arthritis, and has been a huge team effort. Rather than having to rely on blood tests which often do not tell us accurately what is happening in the joint, we can now directly analyse the joint lining, across different types of childhood arthritis and different ages. Our findings show that younger children have different types of immune cells invading their joints compared to older children. Samples from children with arthritis looked different to adult samples, with a different make up of immune cells, blood vessels and distinct connective tissue cells. This suggests that treatments may need to vary depending on age and shows why we can’t just extend studies from adult studies to understand arthritis in children.”
The study was funded by the Medical Research Council, Versus Arthritis, National Institute of Health and Care Research, Great Ormond Street Hospital Charity, amongst others, and delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC).
Instrumental to driving this research forward was Dr Eslam Al-Abadi, a study investigator from the Birmingham Women’s and Children’s Hospital NHS Foundation Trust, who sadly passed away before publication. His incredible efforts in seeking to improve the care of children with this disease are gratefully acknowledged.
