Student Duke-NUS Medical School Singapore, Singapore
Abstract Text: Enthesitis-related arthritis (ERA), a common subtype of juvenile idiopathic arthritis (JIA) in Asia, carries a poor prognosis. Current evidence has implicated CD4+ T cells in its immunopathogenesis. Using a high-dimensional interrogative strategy, we sought to deconvolve the CD4+ T cell landscape in ERA to define immune signatures for augmenting disease management.
We performed mass cytometry on circulating (active ERA, n=30; healthy paediatric controls, n=30) and synovial (active ERA, n=10) CD45+ immune cells using a T-cell centric antibody panel. Cells were stimulated with PMA-ionomycin to capture their cytokine profiles. We analysed the CD4+ T cell compartment and identified subsets differentially present in ERA patients.
Memory CD4+ T cells (CD45RA-CD45RO+) were significantly enriched in the ERA synovium, of which the IFN-γ+TNF-α+ and IL-17A+TNF-α+ effector T cells (Teffs) predominate. CXCR3+CCR6+ CD4+ T cells and memory regulatory T cells (Tregs) were also enriched in the ERA synovium. By further examining the Ki67+ fraction as a surrogate for an antigen-specific response, we detected a significantly lower CXCR3+CCR6+ Treg-Teff ratio in the ERA circulation and synovium. However, this was not seen for the CXCR3-CCR6- Treg-Teff ratio.
The ERA synovial microenvironment is enriched with pathogenic and protective memory CD4+ T cell subsets, which include Teffs bearing the Th1 and Th17 phenotypes and memory Tregs. The lower Ki67+C+ Treg-Teff ratio in ERA suggests reduced suppression of CXCR3+CCR6+ Teffs in disease, which may drive ERA immunopathogenesis. Future work will have to address the relationship between Th1/Th17 and CXCR3+CCR6+ Teffs and the efficacy of Treg suppression in disease.
