Background/Purpose: Anterior uveitis is a form of ocular inflammation associated with rheumatologic disease and can be categorized as granulomatous or non-granulomatous. Whether different ocular manifestations are associated with distinct immune responses, however, remains unclear. Here, we evaluated lymphocyte clonal expansion in granulomatous and non-granulomatous uveitis to determine whether putative antigen-driven T or B cell responses distinguish clinical presentations of ocular inflammation.

Methods: We performed single cell RNA-sequencing (scRNAseq) to obtain an unbiased gene expression survey of aqueous and blood immune cells in subjects with different forms of uveitis. This analysis allowed quantification, cell type identification, and transcriptional profiling of individual lymphocytes within the inflamed eye as compared to cells in circulation, along with T cell receptor and B cell receptor sequencing to determine clonotype distribution.

Results: The majority of aqueous immune cells were CD4 T cells, with smaller contributions of CD8 T cells, B cells, NK cells, and myeloid cells. Analysis of clonal expansion in granulomatous uveitis revealed highly expanded lymphocyte clonotypes, but only in one T or B cell lineage. Coincident with the clonal expansion were transcriptional signatures of T cell receptor signaling and effector differentiation. In contrast, non-granulomatous uveitis was not associated with robust clonal expansion in any T or B cell lineage analyzed.

Conclusion: Here, these data suggest that the clinical presentation of uveitis may be the result of distinct pathogenic mechanisms, with granulomatous inflammation arising from a select few antigen-specific T or B cells. Furthermore, this extensive clonal expansion was seen in a different lymphocyte lineage for each individual, suggesting a distinct antigen-specific response in each patient and highlighting the potential to identify personalized therapeutic targets.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lymphocyte-clonal-expansion-distinguishes-different-forms-of-uveitis/