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The role of T- and B-cells in uveitis, and its implications for more specific targeted treatment.

Uveitis or intraocular inflammation has many causes, such as infections or autoimmunity. The exact pathophysiological mechanism in most forms of autoimmune uveitis has not yet been fully elucidated. In most studies, non-infectious uveitis is considered and treated as a homogeneous group, despite the wide variation in presentation, etiology, pathophysiology and response to treatment. Birdshot uveitis is a rare form of posterior uveitis with strong association with the HLA A29 allele. Previous research has shown that this condition is a T-cell mediated autoimmune condition, triggered by an unknown trigger (melanoma antigen? virus?). Because of the role of T-lymphocytes in birdshot uveitis, a pilot trial was started in which 15 patients with active birdshot uveitis were treated with subcutaneous injections of abatacept (inhibitor of costimulation and activation of T-lymphocytes), with very favorable results. Furthermore, a link with melanoma is also being investigated in this condition. In addition, this doctoral research aims to study the pathophysiology and more specifically the role of T- and B-lymphocytes, by examining cytokines and cells in aqueous humor of patients with various forms of uveitis (birdshot uveitis). , sarcoidosis, undifferentiated intermediate uveitis, HLA B27 uveitis). If the pathophysiology is better known, more targeted treatments can also be sought, as the example of birdshot uveitis demonstrates. Finally, a review article is written on the ophthalmological side effects of immune checkpoint inhibitors (ICI). Checkpoint inhibition has the opposite effect of abatacept (leads to stimulation and activation of T lymphocytes) and can be associated with uveitis (including 'birdshot like uveitis'). The various ocular side effects after ICI may indirectly lead to an improved understanding of the pathophysiology of eye diseases and uveitis in particular. In summary, the aim is to gain more insight into the pathophysiological mechanisms of different forms of non-infectious uveitis, with a view to more targeted treatment.

Date:12 Jul 2022 →  Today
Keywords:T-cell, B-cell, birdshot uveitis, Immune Checkpoint Inhibitor, cytokines
Disciplines:Ophthalmology, Autoimmunity
Project type:PhD project