Experts have pinpointed genetic changes in children with a common form of arthritis to help predict if they will go on to develop a complication that can cause blindness.
The breakthrough could pave the way for more effective screening in patients with juvenile idiopathic arthritis (JIA), which affects an estimated 12,000 youngsters in the UK.
About 30% of children with JIA are thought to be at risk of uveitis, a complication which causes inflammation inside the eye.
Symptoms, such as red eyes and blurred vision, may not be obvious and can develop slowly, and if left untreated uveitis can lead to blindness.
At the moment, NHS guidelines state all children with JIA should have a uveitis screening carried out by a specialist eye doctor withing six weeks of diagnosis, with further appointments usually taking place every three months.
Medics usually identify patients at a higher risk of the complication using a clinical score based on gender, disease subtype and the age at which symptoms started.
This new discovery has the potential to enable clinicians to screen for genetic changes when a young person is first diagnosed with JIA
Now, researchers working in the Cluster Consortium, a UK-wide project led by experts at the UCL Great Ormond Street Institute of Child Health and the University of Manchester, have identified genetic markers in JIA patients which show that some may be more at risk of uveitis than others.
The breakthrough could lead to the development of a blood or saliva test for uveitis to identify those who would benefit most from early intervention.
It could also reduce the need for unnecessary medication and screening appointments in those deemed low risk, according to experts.
Researcher Dr Melissa Tordoff said: “The genetic variants being independent is very important as this tells us that genetics adds risk information not captured by the clinical score to improve the ability to detect uveitis.”
The study analysed the data of 3,079 youngsters with JIA – some 579 of whom also had uveitis – and focused on human leukocyte antigens (HLAs), proteins found on the surface of most cells in the body.
Dr Tordoff added: “The HLA region of the genome is an area which is well known to contribute to autoimmune diseases.
“Many genes in the HLA region code for vital parts of the immune system.
“By looking at the HLA genes in patients with JIA, we found some genetic variants within genes were different in people who had developed uveitis.
“The frequencies of these variants were different between people with uveitis compared to those people without uveitis.”
Lucy Wedderburn, a professor of paediatric rheumatology at UCL and consultant at Great Ormond Street Hospital, said: “This new discovery has the potential to enable clinicians to screen for genetic changes when a young person is first diagnosed with JIA.
“Currently, uveitis is screened for in the clinic – in all children with JIA.
“However, this means that many children who will never get uveitis still have to undergo repeated screening.”
JIA is the most common form of arthritis in children and young people under the age of 16.
According to Versus Arthritis, it impacts about one in 1,000 children in the UK and is more common in girls.
Symptoms include painful, swollen joints, increased tiredness and a fever that keeps returning.
Prof Wedderburn said the team’s discovery “would change how we might treat uveitis, such as giving medicine at an earlier stage”.
“This could mean those who develop uveitis are treated quickly, before the disease can irreversibly damage the eye,” she added.
The idea of identifying uveitis early using a simple test would be groundbreaking – the reduction in taking unnecessary medications, needless time spent at screening appointments and the alleviation of anxiety caused would make an incredible difference to those we support
Dr John Bowes, a Cluster researcher based at the University of Manchester, outlined the team’s future plans.
“Our next step is to repeat this analysis in a separate group of patients to provide us with a robust statistical model,” he said.
“Work can then begin to translate these findings into the clinic to improve the screening process for uveitis in children with juvenile idiopathic arthritis.”
The Cluster Consortium is funded by the Medical Research Council, Versus Arthritis, Great Ormond Street Children’s Hospital Charity, the NIHR, Fight for Sight, and Olivia’s Vision.
Catherine Wright, who has uveitis and is a manager of Versus Arthritis’s People and Families Service, said: “We support thousands of children, young people and their families living with arthritis.
“The idea of identifying uveitis early using a simple test would be ground-breaking – the reduction in taking unnecessary medications, needless time spent at screening appointments and the alleviation of anxiety caused would make an incredible difference to those we support.”
