Cracking the code: How our genetic information might tell us which people with childhood arthritis are at higher risk of eye inflammation

New research from the CLUSTER consortium has shown that by combining genetic and clinical information we may improve our ability to predict which young people with juvenile idiopathic arthritis (JIA) are more likely to develop eye inflammation.

Juvenile idiopathic arthritis and the risk of eye inflammation

Before the anti-TNF revolution, disease activity in young people with juvenile idiopathic arthritis (JIA) was poorly controlled. The impact of JIA on children and young people is still significant. One of the biggest complications for them is eye inflammation, also known as uveitis.

Up to 30% of people with JIA may go on to develop uveitis which can have devastating consequences on the quality of a person's life. It can cause eye pain and blurred vison, and in severe cases if left untreated, it can cause permanent sight loss.

What’s more, when they might develop uveitis can be unpredictable.

The story so far

Previous Versus Arthritis-funded research led from the Experimental Arthritis Treatment Centre for Children showed that for many, a combination of the anti-TNF drug adalimumab, with methotrexate, successfully treated uveitis. However, as not all people with JIA and uveitis benefit from adalimumab, researchers are continuing to investigate new medicines.

But finding the right treatment is only half the story.  

When we give medication is key for preventing irreversible damage, and the unpredictability of uveitis makes this even more tricky.

That’s why researchers at the CLUSTER consortium are looking into which young people with JIA are more likely to develop uveitis.

Currently, risk is measured using a clinical score assessed by a healthcare professional, considering factors such as early onset of the disease and its specific subtype. However, this approach falls short of providing a full picture of who is truly at risk.

As Professor Lucy Wedderburn, Principal Investigator of CLUSTER, explains: “At the moment many children who will never get uveitis still have to undergo repeated uncomfortable screening, taking up NHS and family time, perhaps unnecessarily.”

The CLUSTER researchers are looking to make this risk screening more accurate and tolerable by introducing genetic risk factors.  

The power of genetics

Genetics is the study of the body’s genetic code – the code that tells our cells what to do. Changes to the code can change how the cells function. Some of these changes might contribute to different diseases.

Dr Melissa Tordoff, a CLUSTER researcher,  explains how the team began to zero in on a specific set of genes in an area of interest, called the Human Leukocyte Antigen (HLA) region, “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, researchers found some genetic variants within genes were different in people who had developed uveitis. The number of these variants were different between people with uveitis compared to those people without.

Because the genetic and the clinical risk factors are independent and don’t influence each other they can both be used in the overall risk score.

This means that when a young person is first diagnosed with JIA, we can see if they have these genetic changes or not. This could be through a blood test or a saliva sample for example. With this insight, clinicians could adapt treatment, perhaps giving medicine at an earlier stage.

This could mean those who are at most risk of the condition can be monitored more closely and treated quickly, before the disease can irreversibly damage the eye.

What’s next for someone at risk?

The benefits of knowing who is at risk has multiple benefits. As Dr Tordoff explains, “Those who are high risk for uveitis may have increased frequency of screening for an increased length of time so that ophthalmologists may monitor the patient for uveitis. Those who are defined as low risk may have less frequent screenings over a decreased length of time, which will benefit the patient and family in terms of stress and hospital visits.”

Only when medical guidelines change can doctors start to screen for genetic risk in individuals with JIA and for guidelines to change, researchers need more information.

“Our next step would be to repeat this analysis in a separate group of patients to provide us with a robust statistical model.” says Dr John Bowes.

Following this, the researchers can begin to translate these findings into the clinic. This would involve understanding how best to implement this risk score, listening to patient and clinician points of view, and understanding the barriers to using this in the clinic.

We’re here to help

If you or a family member under the age of 25 has arthritis, we run a Young People and Families Service that provides information and support and puts on a range of events across the country.

Our service helps young people and children by offering advice on how to live well with arthritis, medication and potential treatments, as well as creating a safe space to ask questions, receive information and develop support networks.

If you have any changes to your vision, or your eyes are painful or red, tell your rheumatology team or GP straight away.