{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:51:36Z","timestamp":1790776296598,"version":"4.1.0"},"reference-count":86,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Best Practice &amp; Research Clinical Rheumatology"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1016\/j.berh.2018.02.002","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T23:04:30Z","timestamp":1521587070000},"page":"505-516","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":59,"title":["Systemic juvenile idiopathic arthritis: New insights into pathogenesis and cytokine directed therapies"],"prefix":"10.1016","volume":"31","author":[{"given":"Manuela","family":"Pardeo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Bracaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.berh.2018.02.002_bib1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S0140-6736(07)60363-8","article-title":"Juvenile idiopathic arthritis","volume":"369","author":"Ravelli","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.berh.2018.02.002_bib2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.25.022106.141627","article-title":"Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease","volume":"27","author":"Masters","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib3","series-title":"Textbook of pediatric rheumatology","author":"Cassidy","year":"2015"},{"key":"10.1016\/j.berh.2018.02.002_bib4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.autrev.2012.07.022","article-title":"Systemic juvenile idiopathic arthritis","volume":"12","author":"Martini","year":"2012","journal-title":"Autoimmun Rev"},{"key":"10.1016\/j.berh.2018.02.002_bib5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.clim.2013.03.006","article-title":"Bridging the gap between autoinflammation and autoimmunity","volume":"147","author":"Hedrich","year":"2013","journal-title":"Clin Immunol"},{"issue":"4","key":"10.1016\/j.berh.2018.02.002_bib6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/gene.2012.3","article-title":"Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment","volume":"13","author":"Ravelli","year":"2012","journal-title":"Genes Immun"},{"key":"10.1016\/j.berh.2018.02.002_bib7","first-page":"1133","article-title":"Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis","volume":"34","author":"Behrens","year":"2007","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib8","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0950-3579(98)80018-6","article-title":"Systemic onset juvenile rheumatoid arthritis","volume":"12","author":"Schneider","year":"1998","journal-title":"Bailliere\u2019s Clin Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib10","first-page":"168","article-title":"Radiologic features of systemic onset juvenile rheumatoid arthritis","volume":"22","author":"Lang","year":"1995","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib11","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1136\/annrheumdis-2012-201388","article-title":"It is time to rethink juvenile idiopathic arthritis classification and nomenclature","volume":"71","author":"Martini","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib12","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1002\/art.11300","article-title":"The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families","volume":"48","author":"Ogilvie","year":"2003","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib13","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1002\/art.10882","article-title":"British Paediatric Rheumatology Study Group. Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis","volume":"48","author":"De Benedetti","year":"2003","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib14","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/gene.2008.24","article-title":"Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis","volume":"9","author":"Stock","year":"2008","journal-title":"Genes Immun"},{"key":"10.1016\/j.berh.2018.02.002_bib15","doi-asserted-by":"crossref","first-page":"15970","DOI":"10.1073\/pnas.1520779112","article-title":"HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis","volume":"112","author":"Ombrello","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.berh.2018.02.002_bib16","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1136\/annrheumdis-2016-210324","article-title":"Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications","volume":"76","author":"Ombrello","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib17","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1002\/art.24601","article-title":"Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiophathic arthritis","volume":"6D","author":"Barnes","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"9","key":"10.1016\/j.berh.2018.02.002_bib18","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1084\/jem.20070070","article-title":"Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade","volume":"204","author":"Allantz","year":"2007","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.berh.2018.02.002_bib19","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/ard.2007.079533","article-title":"Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA microarray analysis","volume":"68","author":"Ishikawa","year":"2009","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib20","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrrheum.2011.68","article-title":"Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions","volume":"7","author":"Mellins","year":"2011","journal-title":"Nat Rev Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib21","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1056\/NEJMe1212640","article-title":"A\u00a0new era in the treatment of systemic juvenile idiopathic arthritis","volume":"367","author":"Sandborg","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.berh.2018.02.002_bib22","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1084\/jem.20050473","article-title":"Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade","volume":"201","author":"Pascual","year":"2005","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.berh.2018.02.002_bib23","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095","article-title":"Biologic basis for interleukin-1 in disease","volume":"87","author":"Dinarello","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.berh.2018.02.002_bib24","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1182\/blood.V87.11.4824.bloodjournal87114824","article-title":"Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis","volume":"87","author":"Cazzola","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.berh.2018.02.002_bib25","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1056\/NEJMoa1205099","article-title":"Two randomized trials of Canakinumab in systemic juvenile idiopathic arthritis","volume":"367","author":"Ruperto","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.berh.2018.02.002_bib26","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1002\/art.1780340912","article-title":"Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis","volume":"34","author":"De Benedetti","year":"1991","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1172\/JCI119207","article-title":"Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I: a model for stunted growth in children with chronic inflammation","volume":"99","author":"De Benedetti","year":"1997","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.berh.2018.02.002_bib28","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/art.22175","article-title":"Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system","volume":"54","author":"De Benedetti","year":"2006","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib29","doi-asserted-by":"crossref","first-page":"e107886","DOI":"10.1371\/journal.pone.0107886","article-title":"IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases","volume":"9","author":"Caiello","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.berh.2018.02.002_bib30","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1112802","article-title":"Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis","volume":"367","author":"De Benedetti","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.berh.2018.02.002_bib31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.clim.2012.11.008","article-title":"Phagocyte-derived S100 proteins in autoinflammation: putative role in pathogenesis and usefulness as biomarkers","volume":"147","author":"Kessel","year":"2013","journal-title":"Clin Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib32","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/nm1638","article-title":"Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock","volume":"13","author":"Vogl","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.berh.2018.02.002_bib33","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/art.24349","article-title":"The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis","volume":"60","author":"Frosch","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib34","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1002\/eji.201546092","article-title":"Understanding inflammation in juvenile idiopathic arthritis: How immune biomarkers guide clinical strategies in the systemic onset subtype","volume":"46","author":"Swart","year":"2016","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib35","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/annrheumdis-2011-200598","article-title":"The Toll-like receptor 4 agonist MRP8\/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis","volume":"71","author":"Holzinger","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib36","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1128\/iai.63.10.3966-3972.1995","article-title":"A\u00a0novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock","volume":"63","author":"Okamura","year":"1995","journal-title":"Infect Immun"},{"key":"10.1016\/j.berh.2018.02.002_bib37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/378088a0","article-title":"Cloning of a new cytokine that induces IFN-g production by T cells","volume":"378","author":"Okamura","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.berh.2018.02.002_bib38","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.smim.2013.10.014","article-title":"Interleukin-18, more than a Th1 cytokine","volume":"25","author":"Novick","year":"2013","journal-title":"Semin Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib39","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.4049\/jimmunol.167.5.2879","article-title":"A\u00a0role for IL-18 in neutrophil activation","volume":"167","author":"Leung","year":"2001","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib40","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1002\/art.10389","article-title":"Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: comment on the article by Kawashima, et\u00a0al","volume":"46","author":"Maeno","year":"2002","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib41","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cyto.2012.11.025","article-title":"Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles","volume":"61","author":"Shimizu","year":"2013","journal-title":"Cytokine"},{"key":"10.1016\/j.berh.2018.02.002_bib42","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1007\/s10067-006-0474-0","article-title":"Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis","volume":"26","author":"Jelusi\u0107","year":"2007","journal-title":"Clin Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib43","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clim.2015.06.005","article-title":"Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"160","author":"Shimizu","year":"2015","journal-title":"Clin Immunol"},{"issue":"Suppl. 10","key":"10.1016\/j.berh.2018.02.002_bib44","article-title":"Biomarkers for the diagnosis and the identification of risk of macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA)","volume":"69","author":"Bracaglia","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib45","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/ng.3089","article-title":"An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome","volume":"46","author":"Canna","year":"2014","journal-title":"Nat Genet"},{"key":"10.1016\/j.berh.2018.02.002_bib46","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/ng.3066","article-title":"Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation","volume":"46","author":"Romberg","year":"2014","journal-title":"Nat Genet"},{"key":"10.1016\/j.berh.2018.02.002_bib47","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1067\/mpd.2003.110","article-title":"Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome","volume":"142","author":"Grom","year":"2003","journal-title":"J\u00a0Pediatr"},{"issue":"Suppl. 1","key":"10.1016\/j.berh.2018.02.002_bib48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1546-0096-12-S1-P56","article-title":"Inhibition of natural killer (nk) cell cytotoxicity by interleukin-6: implications for the pathogenesis of macrophage activation syndrome","volume":"12","author":"Cifaldi","year":"2014","journal-title":"Pediatr Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib49","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1002\/art.24750","article-title":"Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis","volume":"60","author":"de Jager","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib50","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1002\/art.38793","article-title":"Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis","volume":"66","author":"Kaufman","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib51","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/rheumatology\/kep418","article-title":"Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis","volume":"49","author":"Vastert","year":"2010","journal-title":"Rheumatology (Oxford)"},{"key":"10.1016\/j.berh.2018.02.002_bib52","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/art.23734","article-title":"Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms","volume":"58","author":"Zhang","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib53","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/art.23199","article-title":"Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis","volume":"58","author":"Hazen","year":"2008","journal-title":"Arthritis Rheum"},{"issue":"Suppl. 1","key":"10.1016\/j.berh.2018.02.002_bib54","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1546-0096-12-S1-P53","article-title":"Mutations of familial hemophagocytic lymphohistiocytosis (FHL) related genes and abnormalities of cytotoxicity function tests in patients with macrophage activation syndrome (MAS) occurring in systemic juvenile idiopathic arthritis (sJIA)","volume":"12","author":"Bracaglia","year":"2014","journal-title":"Pediatr Rheumatol Online J"},{"key":"10.1016\/j.berh.2018.02.002_bib55","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3899\/jrheum.121233","article-title":"Reaching the threshold: a multilayer pathogenesis of macrophage activation syndrome","volume":"40","author":"Strippoli","year":"2013","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12969-015-0055-3","article-title":"Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"13","author":"Boom","year":"2015","journal-title":"Pediatr Rheumatol Online J"},{"key":"10.1016\/j.berh.2018.02.002_bib57","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/art.30128","article-title":"Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series","volume":"63","author":"Nigrovic","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib58","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/art.39407","article-title":"Rate and clinical presentation of macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis treated with canakinumab","volume":"68","author":"Grom","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib59","first-page":"S83","article-title":"A56: macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis treated with tocilizumab","author":"Ravelli","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib60","doi-asserted-by":"crossref","first-page":"712","DOI":"10.3899\/jrheum.140288","article-title":"Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis under treatment with tocilizumab","volume":"42","author":"Yokota","year":"2015","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib61","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1182\/blood-2003-10-3413","article-title":"An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder","volume":"104","author":"Jordan","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.berh.2018.02.002_bib62","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/emmm.200900009","article-title":"Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice","volume":"1","author":"Pachlopnik Schmid","year":"2009","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.berh.2018.02.002_bib63","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1046\/j.1365-2249.2003.02237.x","article-title":"Increased serum levels of interferongamma-iinducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis","volume":"133","author":"Takada","year":"2003","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib64","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jpeds.2011.11.046","article-title":"Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children","volume":"160","author":"Xu","year":"2012","journal-title":"J\u00a0Pediatr"},{"key":"10.1016\/j.berh.2018.02.002_bib65","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1136\/annrheumdis-2015-209020","article-title":"Elevated circulating levels of interferon-\u03b3 and interferon-\u03b3 induced chemokines characterize patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis","volume":"76","author":"Bracaglia","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib66","first-page":"S0091","article-title":"Neutralization of IFN-\u03b3 reverts clinical and laboratory features in a mouse model of macrophage activation syndrome","volume":"12","author":"Prencipe","year":"2017","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.berh.2018.02.002_bib67","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1136\/ard.2010.134254","article-title":"A\u00a0multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)","volume":"70","author":"Quartier","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib68","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1002\/art.38699","article-title":"Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis","volume":"66","author":"Ilowite","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib69","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/S0140-6736(08)60454-7","article-title":"Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial","volume":"371","author":"Yokota","year":"2008","journal-title":"Lancet"},{"key":"10.1016\/j.berh.2018.02.002_bib70","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/art.38296","article-title":"Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study","volume":"66","author":"Vastert","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib71","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.3899\/jrheum.141567","article-title":"Anakinra in systemic juvenile idiopathic arthritis: a single-center experience","volume":"42","author":"Pardeo","year":"2015","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib72","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/art.23437","article-title":"A.\u00a0The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis","volume":"58","author":"Gattorno","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.berh.2018.02.002_bib73","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1136\/ard.2007.076034","volume":"67","author":"Lequerr\u00e9","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib74","first-page":"2071","article-title":"Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis","volume":"31","author":"Verbsky","year":"2004","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib75","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/2050-6511-14-40","article-title":"Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoimflammatory syndromes","volume":"14","author":"Urien","year":"2013","journal-title":"BMC Pharmacol and Toxicol"},{"issue":"9","key":"10.1016\/j.berh.2018.02.002_bib76","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1136\/annrheumdis-2015-207818","article-title":"Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan","volume":"75","author":"Yokota","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib77","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrrheum.2015.179","article-title":"Macrophage activation syndrome in the era of biologic therapy","volume":"12","author":"Grom","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib78","article-title":"Biologic therapy modifies clinical and laboratory features of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis","author":"Schulert","year":"2017","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"10.1016\/j.berh.2018.02.002_bib79","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/annrheumdis-2015-208982","volume":"75","author":"Ravelli","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.berh.2018.02.002_bib80","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/acr.21625","article-title":"Juvenile idiopathic arthritis disease-specific research committee of childhood arthritis rheumatology and research alliance. Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis","volume":"64","author":"DeWitt","year":"2012","journal-title":"Arthritis Care Res"},{"key":"10.1016\/j.berh.2018.02.002_bib81","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1002\/acr.22087","volume":"65","author":"Ringold","year":"2013","journal-title":"Arthritis Care Res"},{"key":"10.1016\/j.berh.2018.02.002_bib82","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/art.38615","article-title":"Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis?","volume":"66","author":"Nigrovic","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib83","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/rheumatology\/kev382","article-title":"Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials","volume":"554","author":"Tarp","year":"2016","journal-title":"Rheumatology"},{"key":"10.1016\/j.berh.2018.02.002_bib84","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/art.40099","article-title":"Proinflammatory cytokine environments can drive Interleukin-17 overexpression by \u03b3\/\u03b4 T cells in systemic juvenile idiopathic arthritis","volume":"69","author":"Kessel","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.berh.2018.02.002_bib85","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V126.23.LBA-3.LBA-3","article-title":"A\u00a0novel targeted approach to the treatment of hemophagocytic lymphohistiocytosis (HLH) with an anti-interferon gamma (IFN\u03b3) monoclonal antibody (mAb), NI-0501: first results from a pilot Phase 2 study in children with primary HLH","volume":"126","author":"Jordan","year":"2015","journal-title":"Blood"},{"issue":"Suppl. 10","key":"10.1016\/j.berh.2018.02.002_bib86","article-title":"Anti-interferon-gamma (IFN\u03b3) monoclonal antibody treatment in a child with NLRC4-related disease and severe hemophagocytic lymphohistiocytosis (HLH)","volume":"67","author":"Bracaglia","year":"2015","journal-title":"Arthritis Rheumatol"}],"container-title":["Best Practice &amp; Research Clinical Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521694218300044?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521694218300044?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T17:17:32Z","timestamp":1761499052000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1521694218300044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":86,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["S1521694218300044"],"URL":"https:\/\/doi.org\/10.1016\/j.berh.2018.02.002","relation":{},"ISSN":["1521-6942"],"issn-type":[{"value":"1521-6942","type":"print"}],"subject":[],"published":{"date-parts":[[2017,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Systemic juvenile idiopathic arthritis: New insights into pathogenesis and cytokine directed therapies","name":"articletitle","label":"Article Title"},{"value":"Best Practice & Research Clinical Rheumatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.berh.2018.02.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}