Age and Activity-Dependent Differences in Intraocular Immune Profile of Chronic Autoimmune Uveitis 2259109

Abstract Introduction Autoimmune uveitis is a chronic inflammatory disorder of the eye. Uveitis relapse occurs in 85% of patients who discontinue medications, necessitating lifelong immunosuppression, yet the pathogenesis of chronic, relapsing eye inflammation is poorly understood. Methods We obtained intraocular aqueous humor (AQH) samples from patients with clinically inactive uveitis (n = 29) or non-inflammatory controls (n = 16) undergoing eye surgery. Olink proteomic profiling and 10X single-cell RNA sequencing were performed on each sample. Results 41% of all uveitis patients displayed subclinical elevation of inflammatory cytokines within their eyes. Even more striking, >85% of children had subclinical immune activity. Single-cell RNA sequencing revealed distinct immune cell populations associated with patient age and clinical disease activity. Namely, we found a higher prevalence of monocytes in adult uveitis, with none detected in pediatric samples. This was supported by proteomic data as well, which showed an association with adult uveitis and myeloid-related inflammatory cytokines. There was no correlation between monocytes and disease activity. In contrast, subclinical immune activity was associated with increased CD8+ T cells, specifically resident memory T cells (TRM), and decreased CD4+ T cell populations. Proteomic analysis confirmed a direct correlation between IL-15, which supports CD8+ T cells and TRM survival, and subclinical disease activity. Conclusion Our results provide further insights into chronic autoimmune uveitis, highlighting distinctions between pediatric and adult disease and activity-dependent immunity in the ocular microenvironment. Funding Source Rheumatology Research Foundation and Joint Biology Consortium microgrant off parent grant NIH/NIAMS P30AR070253 Topic Categories Immune Mechanisms of Human Disease (HUM)