title: Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches.
abstract: Because of its distinct clinical and laboratory features, reflecting systemic inflammation, sJIA can be distinguished from other forms of JIA which usually present as a milder phenotype. The exact pathophysiology of sJIA, however, remains unknown. Profound dysregulation of innate pro- and anti-inflammatory cytokines, and rapid clinical response to cytokine blocking strategies in sJIA patients suggest impaired control mechanisms in innate immune cells contributing to sJIA pathogenesis. Endogenous TLR ligands, such as S100 protein complexes, enhance the pro-inflammatory phenotype. Associations with polymorphisms in cytokine genes and their receptors suggest a genetic component. Furthermore, genetic associations that have been reported in familial hemophagocytic lympohistiocytosis also exist in patients with sJIA-associated macrophage activation syndrome, a severe complication of sJIA. Reported mutations in single genes, however, are too weak to confer sJIA, suggesting a multi-factorial mode of inheritance. We provide an overview of current pathophysiological concepts, state-of-the-art treatment regimens, and unanswered questions in sJIA.
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital Dresden, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Normi
authors.initials: N
authors.lastname: Bruck
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital Dresden, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schnabel
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital Dresden, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: Christian.hedrich@uniklinikum-dresden.de.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Hedrich
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D055501:Macrophage Activation Syndrome / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016207:Cytokines; D005938:Glucocorticoids; D053590:Interleukin 1 Receptor Antagonist Protein; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C541220:canakinumab; C531377:rilonacept; C502936:tocilizumab
keywords: Cytokine; Inflammation; Pathophysiology; Still's disease; Systemic JIA; Treatment