Background/Purpose: Juvenile Idiopathic Arthritis (JIA) is characterized by joint pain and inflammation. Persistent oligoarticular JIA(oligoJIA) is defined by the involvement of up to 4 joints throughout disease course. OligoJIA can progress to an extended form of arthritis (extended-oligoJIA), involving 5 or more joints after the first 6 months of disease. Polyarticular JIA is defined as affecting 5 or more joints in the first 6 months of disease. Over 30% of children with extended-oligoJIA experience uncontrolled disease requiring the use of several immunosuppressive medications even after 8-year follow-up. Moreover, even with current treatment options, 50-60% of children with extended-oligoJIA continue to experience pain, functional disability, disease activity, and impaired quality of life extending into adulthood. There is limited understanding of the cellular composition of inflammatory tissues in JIA, particularly in the affected synovium, which is a major barrier for the identification of disease biomarkers, diagnosis, and therapeutic targeting. The purpose of this study was to identify cell subsets associated with disease progression and severity in the synovium of children with JIA.

Methods: Fourteen synovial tissue biopsies of children with oligoJIA or polyarticular JIA, were collected by ultrasound guided biopsy. Cryopreserved synovial tissue was thawed and enzymatically digested in Liberase and DNAse I, prior to staining with a comprehensive antibody panel encompassing all major immune and non-immune cell types. Matching PBMC samples were also stained for flow analysis from 5 of the individuals. Synovial fluid biomarkers were measured by Luminex.

Results: Flow cytometry analysis revealed significant differences in the cellular composition of B cells, fibroblasts, and T-cell subtypes between PBMC and synovium samples from patients with JIA. Interestingly, we note a significant difference in tissue-specific HLA-DR+ CD8+ activated T cells in polyarticular JIA when compared to oligoJIA. Extending this analysis, we discovered significant correlations of activated and regulatory CD8+ T cell states with Juvenile Arthritis Disease Activity Scores (JADAS). Synovial fluid biomarkers such as IL-18, CD25, IL-6, and IL-23 were similarly correlated to disease activity and the frequency of tissue-specific activated T cells (PD-1+ CD-8+), T peripheral helper cells (HLA-DR+ CD4+), and HLA-DR+ fibroblasts.

Conclusion: With comprehensive flow cytometry analysis, we characterized the heterogenous cellular composition of JIA in both PBMC and disaggregated synovium. We observed increased frequencies of activated T cells specifically within the synovium correlated to disease severity and synovial fluid biomarkers.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/frequency-of-tissue-specific-activated-cd8-t-cells-is-correlated-to-disease-severity-in-juvenile-idiopathic-arthritis/