Thesis defense Jytte Hendrikse

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Uveitis is a rare inflammatory disease of the middle layer of the eye. Despite its rarity, paediatric uveitis is one of the most important causes of visual loss and blindness, especially among a relatively young population.

In approximately 20-35% of cases uveitis is caused by an infection. It is important to identify infectious uveitis in the clinic and to distinguish it from non-infectious uveitis as the treatment regimen is entirely different; whereas treatment in infectious uveitis should be directed at the underlying pathogen, in non-infectious immunosuppressive treatment is essential. The cause of non-infectious uveitis remains uncertain, but evidence supports contributions from both autoimmune and autoinflammatory mechanisms, with different forms of uveitis positioned at various points along this pathogenic spectrum. Genetically polymorphisms in human leukocyte antigen (HLA) genes are associated with different forms of uveitis. Both MS and intermediate uveitis are associated with HLA class II allele HLA-DRB1*15:01 which may in part explain the relation between the two diseases. HLA-DRB1*15:01 uveitis presents with a characteristic uveitis phenotype with signs of intermediate inflammation such as vitreous humour cells, floaters and peripheral capillary leakage on fluorescein angiography, especially following a fern-like leakage pattern.

Although infectious pathogens may not be directly responsible for the chronic inflammation in non-infectious uveitis, pathogens are hypothesized to contribute to changes in the immune system that lead to autoimmune inflammation. In this thesis we found an elevated IgG response to a specific epitope of EBV (AA 402-406) in uveitis patients, indicating that EBV may have a role as potential trigger in some forms of paediatric uveitis, especially in  HLA-DRB1*15:01 positive patients. In MS, EBV has been identified as important trigger for cross-reactivity leading to autoimmunity, specifically in patients with the HLA-DRB1*15:01 allele. These findings point towards a shared aetiology between MS and HLA-DRB1*15:01 positive uveitis.