Work

Synovial Tissue‐Guided Interleukin‐17A Inhibition for Refractory Arthritis in a Patient With Systemic Juvenile Idiopathic Arthritis

Year: 2026

Type: article

Abstract: OBJECTIVE: The objective of this study was to characterize the clinical, immunologic, and synovial tissue features of a patient with a systemic juvenile idiopathic arthritis (sJIA) who carries a novel heterozygous STAT5B loss-of-function variant (p.Gln139Ter) and whose arthritis responded markedly to interleukin-17A (IL-17A) inhibition. METHODS: Patient blood was compared with blood from healthy donors (n = 5) for immunoblotting, phospho-flow cytometry and immune cell profiling. Patient synovial fluid was compared with synovial fluid from seronegative oligoarticular or polyarticular juvenile idiopathic arthritis (oligo/poly JIA) (n = 5-6) for immune cell profiling. Patient synovial tissue was compared with synovial tissue from children with oligo/poly JIA (n = 11) using Xenium spatial transcriptomics. RESULTS: T cells showed markedly increased IL-17A production (z score = 34.5) and reduced FOXP3 expression (z score = -2.25) in regulatory T cells. Spatial transcriptomics revealed T helper 17 (Th17) cells distributed diffusely throughout the patient's synovium, in contrast to JIA controls in which Th17 cells were largely restricted to tertiary lymphoid structures (TLS) (z score = 3.08). The patient's severe arthritis, previously refractory to IL-1 and IL-6 blockade, improved markedly after IL-17A inhibition. CONCLUSION: STAT5B haploinsufficiency may contribute to an sJIA phenotype characterized by Th17/IL-17 dysregulation and an altered distribution of Th17 cells outside TLS. Integrated genetic, functional, and spatial tissue analyses may help identify therapeutic targets in refractory pediatric arthritis.

Source: Arthritis & Rheumatology

DOI: 10.1002/art.70395