Young people donate tissue samples to unlock mysteries of arthritis

Published in Science Translational Medicine, for the first time scientists have been able to see what happens in the inflamed joints of children with arthritis. This has uncovered the unique architecture of cells and signals inside the joint, giving insight into why treatments affect children differently.

Juvenile idiopathic arthritis (JIA) 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. Whilst treatments are available to manage the condition, and in some cases achieve remission, there is no cure.

Treatments don’t work in the same way for every child, and it can take time to find out what works, suggesting there are hidden differences between individuals that researchers are only beginning to understand.

To understand the condition more deeply, scientists need to explore tissue samples but justifying performing biopsies with young children can be difficult. However, families advocated for the potential of this study, agreeing 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. These samples were then analysed with advanced imaging and gene-profiling technologies.

Detailed maps of the joints revealed differences between children of different ages and cell changes in those with more severe disease. These unique cellular fingerprints may help researchers understand why some treatments work better for some children, and not others. The joints of children with arthritis looked significantly different to those with adults, demonstrating the need to understand arthritis in children better.

One of the children who took part in the study was Aurelia, who was diagnosed with arthritis after injuring her knee while on holiday.

Aurelia, from Twickenham in southwest London, was referred to the specialist arthritis service at GOSH.

Her mum Emily said: “Aurelia is a sporty child and loves art, drama, music and ballet. We noticed pain and swelling of her knee while on holiday. We thought perhaps she had injured it playing, but when this didn't get better and she was struggling to walk, we realised something else was wrong. She was referred to the Rheumatology team at GOSH who diagnosed her with arthritis. This came as a bit of a shock given how active she is!

“They offered her a steroid injection in her knee under general anaesthetic to alleviate the symptoms. The team asked if we were happy for her to take part in this research study and collect some tissue samples at the same time.

“We were keen for her to be involved, as there’s still a lot of unknowns with arthritis in children, and not all treatments can work. Given that she was already having an anaesthetic, and it wasn’t an additional operation for her, it was a good opportunity for researchers to take samples and to be better able to study the conditions. We hope the study will help other families with children in similar positions to us.

“Since having the steroid injection and taking part in an intensive two week ‘physio school’, Aurelia has managed her symptoms well and almost has her full range of movement back. She recently won her running race at sports day which is thanks to all the incredible team at GOSH. From the nurses to the physios, from the anaesthetists to the doctors, everyone was so supportive and fantastic. So many people were involved in her care and GOSH is such a special place.”

Another child who took part in the study was Albert from Southend-on-Sea in Essex, who was diagnosed with JIA four years ago.

His mum Ashley said: “We noticed that Albert’s knees were swollen, and often painful and stiff in the mornings. After having some blood tests and scans at our local hospital, Albert was diagnosed with JIA and transferred to the rheumatology team at GOSH.

“We’d never heard of JIA before and didn’t know what this would mean for Albert, as he’s really active and plays for the local football team. He’s been well-cared for at GOSH and the team are really helpful. He’s had several steroid injections to manage his symptoms, but he might have to try an alternative treatment in the future if the injections don’t work as well.

“We were happy to take part in the study as we hope it will give our family, others, and researchers more information about JIA and the potential to develop new treatments in the future. As Albert was already having a steroid injection and the study didn’t require him having another procedure, it was a great opportunity for us to take part in.”

Professor Lucy Wedderburn, Consultant of Paediatric Rheumatology at GOSH and University College London Great Ormond Street Institute of Child Health, and senior author on the paper, 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 and the Kennedy Trust.

A wider programme of work, made possible by a Medical Research Council partnership award known as Tissue Research in Childhood Arthritis (TRICIA), supports the infrastructure needed for multi-centre tissue research of the joint. In future, it is hoped that a larger study, involving more centres will allow researchers to delve deeper into the remaining questions about how best to tailor treatments for individual patients.

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.