Clinicomolecular Identification of Conserved and Individualized Features of Granulomatous Uveitis.
Ophthalmol Sci
; 1(1)2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-35937550
ABSTRACT
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 OutcomesMeasures:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article