YU-TSAN LINCHEN-TI WANGGershwin M.E.BOR-LUEN CHIANG2020-12-182020-12-1820111568-9972https://www.scopus.com/inward/record.uri?eid=2-s2.0-79957643739&doi=10.1016%2fj.autrev.2011.02.001&partnerID=40&md5=a3cd6d25dbfe97eaaf5dac3c429ac89bhttps://scholars.lib.ntu.edu.tw/handle/123456789/527260Juvenile 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. ? 2011 Elsevier B.V.[SDGs]SDG3autoantigen; disease modifying antirheumatic drug; gamma interferon; glucocorticoid; heat shock protein; interleukin 1; interleukin 10; interleukin 17; interleukin 18; interleukin 6; interleukin 6 antibody; nonsteroid antiinflammatory agent; protein S 100; recombinant interleukin 1 receptor blocking agent; transcription factor FOXP3; tumor necrosis factor inhibitor; adaptive immunity; autoimmune disease; cartilage; clinical feature; comparative study; cytokine production; disease classification; environmental factor; genetic association; human; immunological tolerance; infection; innate immunity; juvenile rheumatoid arthritis; laboratory test; macrophage; macrophage activation syndrome; monocyte; neutrophil; pathogenesis; phagocyte; polyarthritis; regulatory T lymphocyte; review; risk factor; synovitis; T lymphocyte activation; Th1 cell; Th17 cell; treatment planning; treatment response; Adaptive Immunity; Arthritis; Arthritis, Juvenile Rheumatoid; Autoantigens; Cytokines; Humans; Immunity, Innate; Phagocytes; Secretory Pathway; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th1-Th2 Balancereview10.1016/j.autrev.2011.02.001213206442-s2.0-79957643739