Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes

Area of Science:

• Ophthalmology
• Immunology
• Genomics

Background:

• Uveitis encompasses diverse ocular inflammatory conditions often inadequately treated with current therapies.
• Identifying distinct pathophysiologic subtypes is crucial for developing targeted uveitis treatments.

Purpose of the Study:

• To apply single-cell transcriptional and immune receptor profiling to ocular fluid biopsies.
• To define pathophysiologic subtypes of uveitis based on immune cell profiles.

Main Methods:

• Single-cell RNA sequencing and immune receptor repertoire sequencing were performed on ocular fluid from 23 uveitis patients.
• Analysis focused on transcriptional profiles and immune cell populations to identify disease endotypes.

Main Results:

• A subset of ocular T-cells showed local clonal expansion, suggesting antigen-driven uveitis in some cases.
• HLA-B27 associated acute anterior uveitis (HLA-B27 AAU) infiltrates were enriched in myeloid cells and innate immune pathways.
• Chronic uveitis displayed prominent adaptive immune cells and distinct transcriptional programs, differentiating it from acute forms.

Conclusions:

• Immunologic features, including cell type and pathway enrichment, distinguish uveitis subtypes.
• Clinical features correlate with immune cell profiles, adding another layer of variability.
• Deep transcriptional profiling of ocular immune cells offers a powerful approach to reveal uveitis endotypes and guide future therapeutic strategies.