A Novel Heterozygous STAT5B Loss-of-Function Variant Associated with Interleukin-17A-Responsive Systemic Juvenile Idiopathic Arthritis-like Disease

Synovial fluid CD4+ T cells showed markedly increased interleukin (IL)-17A production and reduced FOXP3 and CD25 expression in regulatory T cells (Tregs). Spatial transcriptomics revealed 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). The patient's severe arthritis, previously refractory to IL-1 and IL-6 blockade, improved markedly after interleukin-17A inhibition.

Conclusion. STAT5B haploinsufficiency can present as an sJIA-like phenotype with Th17/IL-17 dysregulation and extra-TLS Th17 distribution. Integrated genetic, functional, and spatial tissue analyses can guide targeted therapy in refractory pediatric arthritis.