Mycobacterium Tuberculosis-Associated Uveitis: Infection and Autoimmunity

The pathophysiology of Mycobacterium tuberculosis (_Mtb_)-associated uveitis is not entirely understood, and in consequence, the diagnosis and the treatment of _Mtb_-associated uveitis are challenging. The studies included in this thesis aim to increase our knowledge of this debilitating ocular disorder and aim to develop specific biomarkers for its diagnosis. The studies performed in this thesis further indicate that _Mtb_ infection plays a crucial role in a significant proportion of patients "with uveitis of undetermined cause" but positive QFT reaction. Two specific clinical manifestations were recognized in patients with uveitis of undetermined cause and positive QFT in the Netherlands, a country not endemic to _Mtb_. QFT positive patients with uveitis might benefit from ATT, despite the absence of systemic signs of active TB. In Indonesia, infectious uveitis was the most common type of uveitis and uveitis in the setting of systemic TB was one of its major causes. Further, _Mtb_ infected RPE cells dominantly showed interferon signaling canonical pathway and network. In the peripheral blood, type 1 IFN gene signature score stratified _Mtb­_-associated uveitis in three types. These findings might form the basis for a prospective trial with ATT and/or corticosteroids. Lastly, we found no evidence that antibodies against retinal antigens are involved in the pathogenesis in _Mtb_-associated uveitis, and we assume that -if autoimmune processes are involved- a cellular response is more likely