New insights into childhood uveitis point to links with viruses, genetics and the immune system

Childhood uveitis, a rare but potentially sight-threatening inflammation of the eye, may be far more connected to systemic disease and previous viral infections than previously understood. PhD research by Jytte Hendrikse (UMC Utrecht) sheds light on the complex causes of childhood uveitis and could pave the way for more personalized treatment and earlier detection of related diseases.

Childhood uveitis – affecting around 1 in 1,000 children in the Netherlands – is a rare group of inflammatory eye diseases with diverse clinical presentations and treatment needs. Although it can threaten vision, research has mainly focused on uveitis associated with juvenile idiopathic arthritis, leaving other forms less well understood.

In 20-35 percent of cases, uveitis is caused by an infection. Distinguishing infectious from non-infectious uveitis is crucial because treatment strategies differ fundamentally: infectious uveitis requires therapy targeting the underlying pathogen, whereas non-infectious forms are treated with immunosuppressants. The causes of non-infectious uveitis remain unclear, but both autoimmune and autoinflammatory mechanisms are thought to play a role.

In her PhD thesis, Jytte Hendrikse, MD (Department of Ophthalmology, UMC Utrecht) investigated infectious triggers, genetic risk factors and immune mechanisms involved in childhood uveitis. Her findings suggest that the disease extends beyond the eye and shares biological pathways with systemic autoimmune disorders, including multiple sclerosis (MS).

Studies by Jytte confirmed that infections remain an important cause of childhood uveitis. Approximately one-third of cases can be linked to pathogens such as Toxoplasma gondii, herpes viruses, cytomegalovirus and tuberculosis. Correct diagnosis is essential because treatment differs markedly between infectious and non-infectious disease.

The study also highlights the importance of screening for tubulointerstitial nephritis and uveitis (TINU) syndrome, which affects both the eyes and kidneys. While visual outcomes were generally good, nearly one-third of patients developed chronic kidney disease within two years, emphasizing the need for early diagnosis and multidisciplinary care.

Another important finding concerns the relationship between uveitis and MS. Hendrikse identified a subgroup of patients carrying the HLA-DRB1*15:01 genetic variant, a known risk factor for MS. These children displayed a distinctive form of eye inflammation and may benefit from tailored treatment strategies that consider their elevated neurological risk.

The thesis further provides evidence that Epstein-Barr virus (EBV), the cause of glandular fever, may contribute to autoimmune eye disease. Children with uveitis showed strong immune responses to specific EBV proteins, particularly those carrying the HLA-DRB1*15:01 risk variant. This supports growing evidence that EBV may trigger autoimmune disease through immune cross-reactivity, causing the body to attack its own tissues.

Researchers also found indications that both the gut microbiome and the bacteria living on the eye surface are altered in children with uveitis, potentially contributing to chronic inflammation.

Together, these findings support a broader view of childhood uveitis as a disease involving interactions between genetics, infections, immunity and systemic health. Improved understanding of these mechanisms could lead to earlier diagnosis, more personalized treatment and better outcomes for affected children.