by University College London
A set of genes that could be used to help doctors predict which children will respond well to treatment for juvenile idiopathic arthritis (JIA) has been identified by researchers at UCL and Great Ormond Street Hospital for Children (GOSH), who are part of the CLUSTER Consortium.
JIA is a childhood immune disease where the immune system attacks the body, in particular the lining of the joints. It is the most common type of arthritis in children under 16 and includes symptoms such as joint pain, swelling and stiffness.
For the new study, published in Annals of the Rheumatic Diseases, researchers generated data about how active certain genes were (gene expression) in the blood cells of 97 children with JIA to see which patients responded best to one of the most commonly prescribed and effective medications for the condition, methotrexate (MTX). They then validated their results in a further 73 children with JIA.
The researchers focused on a group of genes involved in the interferon pathway, which helps to control the immune system.
They found that children whose interferon-driven genes were more active before treatment were more likely to get better when given methotrexate.
However, children with lower gene expression of interferon-driven genes didn’t respond as well.
The researchers hope that their findings will enable clinicians to choose the best medicine for each child more quickly and accurately.
Senior author, Professor Lucy Wedderburn (UCL Great Ormond Street Institute of Child Health and GOSH) said, “Although many treatments for JIA are available, such as MTX, the response to MTX treatment is not always successful in every child, and choosing which is the right medicine for a particular child is not easy.
“Therefore, it is important to find indicators or ‘biomarkers’ that can tell the doctors and health care team which drug treatment is most likely to work for each child depending on their disease status.”
For the study, the research team followed 123 children with JIA in the UK and used data from a further group of 47 children from the U.S. who had not yet started any strong arthritis medicines.
They took blood samples before the treatment had started and used RNA sequencing to measure the gene activity in different types of immune cells.
They then tracked the patients over the course of 6 months to assess which genes were linked to how well the children improved after MTX treatment.
The researchers found that just five genes could help predict who would respond well to MTX.
Professor Wedderburn added, “Our findings mean that in the future, a simple blood test could help doctors know early if MTX will work. This means that children could get the right treatment faster, avoid side effects, and stay healthier.”
More information: Melissa Kartawinata et al, Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis, Annals of the Rheumatic Diseases (2025). DOI: 10.1016/j.ard.2025.03.007
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