Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches

Copyright © 2015 Elsevier Inc. All rights reserved.

Détails bibliographiques
Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 159(2015), 1 vom: 09. Juli, Seite 72-83
Auteur principal: Bruck, Normi (Auteur)
Autres auteurs: Schnabel, Anja, Hedrich, Christian M
Format: Article en ligne
Langue:English
Publié: 2015
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Journal Article Review Cytokine Inflammation Pathophysiology Still's disease Systemic JIA Treatment Antibodies, Monoclonal Antibodies, Monoclonal, Humanized plus... Antirheumatic Agents Cytokines Glucocorticoids Interleukin 1 Receptor Antagonist Protein Recombinant Fusion Proteins Tumor Necrosis Factor-alpha canakinumab 37CQ2C7X93 rilonacept 8K80YB5GMG tocilizumab I031V2H011
Description
Résumé:Copyright © 2015 Elsevier Inc. All rights reserved.
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
Description:Date Completed 24.08.2015
Date Revised 18.03.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.04.018