Postdoctoral Trainee Boston Children's Hosp. Boston, Massachusetts, United States
Disclosure(s):
Eamon Winden, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
