Uncovering the link between arthritis and sight loss in children

Brief lay background

Juvenile Idiopathic Arthritis (JIA), characterized as joint swelling that lasts at least six weeks in under 16-year-olds affects one in 1,000 children in the UK. For unknown reasons, some JIA patients also develop uveitis, an inflammatory disorder of the eye.

In a select group of JIA-uveitis patients, their disease does not respond to therapy, leading to long-term loss of sight. Loss of sight in childhood leads to significant negative impact on quality of life and a reduction in global childhood development.

To improve treatment outcomes and clinical monitoring of at-risk children, there is a major unmet need for studies that investigate why some JIA patients develop uveitis and others do not.

What problem/knowledge gap does it help address

Current treatment strategies for JIA-uveitis involve blocking the production of inflammatory cells. However, there is evidence that JIA-uveitis development could be driven by a population of white blood cells called B-cells.

During infections, B-cells produce molecules called antibodies, which help clear bacteria and viruses from the body. However, in children with JIA, the production of antibodies that interact with the proteins that package our DNA, are associated with uveitis development.

Early onset of JIA (at approx. 2-3 years of age) is also another risk factor for JIA-uveitis; studies have shown that in early onset JIA there are changes in the ‘B-cell signature’ compared to children with later onset JIA.

Aim of the research project

To test  the hypothesis that uveitis development in JIA patients is driven by changes to B-cell function.

Key procedures/objectives

1. Identify a uveitis-specific B-cell immunological fingerprint in JIA-patients.
2. Interrogate mechanistic targets underlying B-cell dysfunction in JIA-uveitis patients.
3. Assess the role of B-cell-driven immunopathology in experimental autoimmune uveitis.

Potential impact on people with sight loss

If successful, this project has the potential to improve JIA-uveitis treatment. Importantly, there are already B-cell targeting drugs used for treatment of other inflammatory disorders. This project could provide evidence for the wider application of these drugs to JIA-uveitis and could also identify a ‘uveitis fingerprint’ in peripheral blood to identify ‘at risk’ patients. This could reduce screening times for all JIA patients, which leads to many hours of missed school time.