Deciphering the impact of childhood non-infectious uveitis: a clinical, genetic and immunological framework for personalized medicine

Abstract

Uveitis is a severe and potentially blinding eye disease and is characterized by inflammation of the iris, choroid and retina. Uveitis can lead to complications resulting in severe vision loss or even blindness. Over the past years novel treatments and guidelines have been developed. Therefore, in the first of part of this thesis, we aimed to gain new insights in the disease burden, clinical course and prognosis of children with uveitis. We found that the number of complications and blind eyes have decreased over the past years. Furthermore, we describe a new treatment strategy for children with severe non-anterior uveitis. In addition, we have found that the prevalence of severe fatigue in children and adolescents with non-infectious uveitis is similar to that of their healthy peers. However, children who are severely fatigued have a lower health-related quality of life. In the second part of this thesis, we used new techniques to further unravel the disease mechanism to facilitate tools that will enable personalized medicine. Our data shows heterogeneity in B cells in patients with juvenile idiopathic arthritis (JIA) associated uveitis. This suggests a role for specific B cell subsets in the etiology of uveitis in JIA. In addition, we examined HLA associations. Our results show that that clinically different forms of uveitis have the same HLA associations. These genetic predispositions may influence antigen presentation. We also examined whether we can predict treatment response with proteins in the blood. Using a protein profile in the blood at diagnosis, we were able to predict treatment response during follow-up. This is a step towards the development of more patient-centered care.