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Updated: Sep 2, 2025
Primed Mycobacterial Uveitis PMU as a Model for Post-Infectious Uveitis
Published on: December 17, 2021
Clinicomolecular Identification of Conserved and Individualized Features of Granulomatous Uveitis
Lynn M Hassman1,2, Michael A Paley3,2, Ekaterina Esaulova4
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110.
Objective:
To identify molecular features that distinguish individuals with shared clinical features of granulomatous uveitis.
Design:
Cross-sectional, observational study.
Participants:
Four eyes from patients with active granulomatous uveitis.
Methods:
We performed single-cell RNA-sequencing with antigen-receptor sequence analysis to obtain an unbiased gene expression survey of ocular immune cells and identify clonally expanded lymphocytes.
Main Outcomes Measures:
For each inflamed eye, we measured the proportion of distinct immune cell types, the amount of B or T cell clonal expansion, and the transcriptional profile of T and B cells.
Results:
Each individual had robust clonal expansion arising from a single T or B cell lineage, suggesting distinct, antigen-driven pathogenic processes in each patient. This variability in clonal expansion was mirrored by individual variability in CD4 T cell populations, whereas ocular CD8 T cells and B cells were more transcriptionally similar between patients. Finally, ocular B cells displayed evidence of class-switching and plasmablast differentiation within the ocular microenvironment, providing additional support for antigen-driven immune responses in granulomatous uveitis.
Conclusions:
Collectively, our study identified both conserved and individualized features of granulomatous uveitis, illuminating parallel pathophysiologic mechanisms, and suggesting that future personalized therapeutic approaches may be warranted.
