Recent advances in our understanding of the pathogenesis of juvenile idiopathic arthritis and their potential clinical implications.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) comprises systemic and non-systemic forms of chronic childhood arthritis diagnosed prior to age 16. Significant improvement in treatment outcomes has been witnessed since the introduction of biologics. In particular, advances in research in the area of multidimensional interrogation and network analysis have facilitated understanding of the complex cacophony of components orchestrating disease immunopathogenesis. Areas covered: In this review, we will examine the scientific advances that have augmented our understanding of JIA pathogenesis, focusing on the progress made in systemic, poly, and oligo JIA in four major aspects: (a) unraveling the pathogenic mechanisms, (b) disease classification, (c) therapeutic selection, and (d) decision for withdrawal of medications after achieving remission. Expert commentary: Dysregulation of innate immune cell physiology and function in sJIA will be highlighted. MicroRNAs contribute to monocyte/macrophage polarization with resulting consequences on macrophage activation syndrome development. The involvement of neutrophils, a major source of S100A8/9/12, in the active inflammatory phase of sJIA is compelling. In non-sJIA, circulating CD4 subsets in T effector and regulatory compartments possessing a strong synovial T-cell receptor coverage and disease activity correlation, acted as an accessible reservoir of pathogenic cells exploitable for clinical management.