Innately Adaptive or Truly Autoimmune: Is There Something Unique About Systemic Juvenile Idiopathic Arthritis?

Abstract

Systemic juvenile idiopathic arthritis (JIA) is a form of arthritis in childhood that is initially dominated by innate immunity-driven systemic inflammation and is thus considered a polygenic autoinflammatory disease. However, systemic JIA can progress toward an adaptive immunity-driven afebrile arthritis. Based on this observation of biphasic disease progression, a "window of opportunity" for optimal, individualized and target-directed treatment has been proposed. This hypothesis requires testing, and in this review we summarize current evidence regarding molecular factors that may contribute to the progression from an initially predominantly autoinflammatory disease phenotype to autoimmune arthritis. We consider the involvement of innately adaptive γδ T cells and natural killer T cells that express γδ or αβ T cell receptors but cannot be classified as either purely innate or adaptive cells, versus classic B and T lymphocytes in this continuum. Finally, we discuss our understanding of how and why some primarily autoinflammatory conditions can progress toward autoimmune-mediated disorders over the disease course while others do not and how this knowledge may be used to offer individualized treatment.Dr. Foell's work was supported by the DFG (project FO 354/11-1).

Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms

“…Anakinra inhibits the proinflammatory cytokines interleukin (IL)-1α and IL-1β and has been used with some success to treat macrophage activation syndrome caused by various inflammatory conditions, 4,5 and in several small studies in patients with COVID-19. 6,7 Here we support the rationale for targeting hyperinflammation in COVID-19 with anakinra and comment on different aspects of its use, patient selection, dosing, and outcome measures.…”

“…This finding could account for the rapid onset of clinical and imaging findings. 7 Since the patient showed altered clotting (prolonged prothrombin time and activated partial thromboplastin time, and increased D-dimer) in the presence of anti phospho lipid antibodies and pathologically reduced serum complement levels, immune complex genera tion and deposition could, in addition to endothelial activation through IL-1, have contributed to activation of the complement and clotting cascades. 8 Indeed, post infectious antiphospholipid syn drome with thrombo embolism has been reported in the context of COVID-19.…”

“…The dose and route of administration of anakinra is especially relevant given its short plasma half-life, with both intravenous and subcutaneous routes being considered. 6,7 While a short half-life is beneficial in limiting the drug's duration of action in case of adverse events, it also leads to large peak-trough fluctuations with an intravenous formulation. Variation in dosing needs to be minimised to ensure constant and adequate bioavailability, and to avoid a detrimental rebound…”

The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

“…Systemic-onset juvenile idiopathic arthritis (SoJIA) is an autoinflammatory disorder of unknown etiology, characterized by spiking fever, lymphadenopathy, and generalized skin rash. Although it has been classified into one of the seven JIA subtypes 16 , the pediatric counterpart to adult-onset Still’s disease is considered a prototypic polygenic autoinflammatory disease distinct from other variants of JIA 17 . Affected children present with a high fever complicated by cytokine storm and then develop idiopathic arthritis during the course of the disease.…”

Roles of Interactions Between Toll-Like Receptors and Their Endogenous Ligands in the Pathogenesis of Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease

“…Changes in the adaptive immune system in systemic JIA and AOSD, and the effects of IL-1 and IL-18 on T cell differentiation and activity have been established, suggesting that innate and adaptive immune responses are linked in both disorders ( 28 ). The frequencies of circulating Th17 cells were elevated and correlated with disease activity in patients with AOSD, and the proportions of IFN-γ- and IL-17-producing CD4+T cells and IL-17-producing CD3+CD4- T cells were increased in systemic JIA ( 29 , 30 ).…”