title: The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis.
abstract: Juvenile idiopathic arthritis (JIA) has had a long and difficult problem with classification. It is clearly a heterogeneous and multi-factorial autoimmune disease but all too often the distinctions among subtypes were unclear. In fact, there is now increasing evidence of a distinct pathogenesis of oligo/polyarticular JIA compared to systemic JIA. Oligo/polyarticular JIA is an antigen-driven lymphocyte-mediated autoimmune disease with abnormality in the adaptive immune system. Cartilage-derived auto-antigens activate autoreactive T cells including Th1 and Th17 cells with production of pro-inflammatory cytokines IFN-γ and IL-17. On the other hand, the inhibition of regulatory T (Treg) cells including natural Foxp3(+) Treg and self-heat shock protein-induced Treg cells with decreased anti-inflammatory cytokine IL-10 results in the loss of immune tolerance. Imbalance between autoreactive Th1/Th17 and Treg cells leads to the failure of T cell tolerance to self-antigens, which contributes to the synovial inflammation of oligo/polyarticular JIA. By contrast, systemic JIA is an autoinflammatory disease with abnormality in the innate immune system. A loss of control of the alternative secretory pathway leading to aberrant activation of phagocytes including monocytes, macrophages and neutrophils seems to be involved in the release of pro-inflammatory cytokines IL-1, IL-6, IL-18 and pro-inflammatory S100-proteins, which contribute to the multisystem inflammation of systemic JIA. Markedly distinct pathogenesis of oligo/polyarticular JIA and systemic JIA implies that they might need different treatment strategies.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Tsan
authors.initials: YT
authors.lastname: Lin
authors.forename: Chen-Ti
authors.initials: CT
authors.lastname: Wang
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D056704:Adaptive Immunity; D001168:Arthritis / Q000145:classification / Q000276:immunology*; D001171:Arthritis, Juvenile / Q000145:classification / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D010586:Phagocytes / Q000276:immunology*; D055571:Secretory Pathway / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058408:Th1-Th2 Balance
chemical_list: D001324:Autoantigens; D016207:Cytokines