{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:12:15Z","timestamp":1792023135200,"version":"4.4.0"},"reference-count":93,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R013926\/1"],"award-info":[{"award-number":["MR\/R013926\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","award":["VS0518"],"award-info":[{"award-number":["VS0518"]}],"id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Birmingham Biomedical Research Centre"],"award-info":[{"award-number":["Birmingham Biomedical Research Centre"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Great Ormond Street Biomedical Research Centre."],"award-info":[{"award-number":["Great Ormond Street Biomedical Research Centre."]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Manchester Biomedical Research Centre"],"award-info":[{"award-number":["Manchester Biomedical Research Centre"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Moorfields Biomedical Research Centre"],"award-info":[{"award-number":["Moorfields Biomedical Research Centre"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["MR\/R013926\/1"],"award-info":[{"award-number":["MR\/R013926\/1"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ard.eular.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Rheumatic Diseases"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1136\/ard-2022-222553","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T13:25:15Z","timestamp":1670246715000},"page":"449-456","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis"],"prefix":"10.1016","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-1429","authenticated-orcid":false,"given":"Lucy R","family":"Wedderburn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athimalaipet V","family":"Ramanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9487-0511","authenticated-orcid":false,"given":"Adam P","family":"Croft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-9262","authenticated-orcid":false,"given":"Kimme L","family":"Hyrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Dick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1136\/ard-2022-222553_bib1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"10.1136\/ard-2022-222553_bib2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1056\/NEJMra1909094","article-title":"Reframing immune-mediated inflammatory diseases through signature cytokine hubs","volume":"385","author":"Schett","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1136\/ard-2022-222553_bib3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41584-021-00726-8","article-title":"Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach","volume":"18","author":"Tanaka","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib4","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 Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib5","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1093\/rheumatology\/keab714","article-title":"Incidence and prevalence of juvenile idiopathic arthritis in the United Kingdom, 2000-2018: results from the clinical practice research Datalink","volume":"61","author":"Costello","year":"2022","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41584-021-00590-6","article-title":"Biological classification of childhood arthritis: roadmap to a molecular nomenclature","volume":"17","author":"Nigrovic","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41572-021-00332-8","article-title":"Juvenile idiopathic arthritis","volume":"8","author":"Martini","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"10.1136\/ard-2022-222553_bib8","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1002\/art.42113","article-title":"A comparison of international League of associations for rheumatology and pediatric rheumatology international trials organization classification systems for juvenile idiopathic arthritis among children in a Canadian arthritis cohort","volume":"74","author":"Lee","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/art.40884","article-title":"2019 American College of Rheumatology\/Arthritis foundation guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis","volume":"71","author":"Ringold","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/art.42037","article-title":"2021 American College of rheumatology guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for Oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis","volume":"74","author":"Onel","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jpeds.2017.08.048","article-title":"Characteristics and changes of pediatric therapeutic trials under the best pharmaceuticals for children act","volume":"192","author":"Avant","year":"2018","journal-title":"J Pediatr"},{"key":"10.1136\/ard-2022-222553_bib12","author":"European, Commission"},{"key":"10.1136\/ard-2022-222553_bib13","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1136\/annrheumdis-2013-204168","article-title":"Impact of the European paediatric legislation in paediatric rheumatology: past, present and future","volume":"72","author":"Ruperto","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s11096-021-01303-5","article-title":"Regulating pediatric off-label uses of medicines in the EU and USA: challenges and potential solutions : comparative regulation framework of off label prescriptions in pediatrics: a review","volume":"44","author":"Guidi","year":"2022","journal-title":"Int J Clin Pharm"},{"key":"10.1136\/ard-2022-222553_bib15","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1056\/NEJM200003163421103","article-title":"Etanercept in children with polyarticular juvenile rheumatoid arthritis. pediatric rheumatology collaborative Study Group","volume":"342","author":"Lovell","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1136\/ard-2022-222553_bib16","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/1529-0131(199707)40:7<1202::AID-ART3>3.0.CO;2-R","article-title":"Preliminary definition of improvement in juvenile arthritis","volume":"40","author":"Giannini","year":"1997","journal-title":"Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.semarthrit.2016.06.001","article-title":"Treatment prescribing patterns in patients with juvenile idiopathic arthritis (JIA): analysis from the UK childhood arthritis prospective study (CAPS)","volume":"46","author":"Davies","year":"2016","journal-title":"Semin Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib18","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.semarthrit.2016.10.008","article-title":"Efficacy of biologic therapy across individual juvenile idiopathic arthritis subtypes: a systematic review","volume":"46","author":"Davies","year":"2017","journal-title":"Semin Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib19","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.berh.2018.02.002","article-title":"Systemic juvenile idiopathic arthritis: new insights into pathogenesis and cytokine directed therapies","volume":"31","author":"Pardeo","year":"2017","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib20","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1093\/rheumatology\/keab113","article-title":"A dysregulated interleukin-18-interferon-\u03b3-CXCL9 axis impacts treatment response to canakinumab in systemic juvenile idiopathic arthritis","volume":"60","author":"Hinze","year":"2021","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib21","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/rheumatology\/ket152","article-title":"A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8\/14 protein","volume":"52","author":"Moncrieffe","year":"2013","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib22","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1167\/iovs.15-17066","article-title":"Elevated S100A8\/A9 and S100A12 serum levels reflect intraocular inflammation in juvenile idiopathic arthritis-associated uveitis: results from a pilot study","volume":"56","author":"Walscheid","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1136\/ard-2022-222553_bib23","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jama.2010.375","article-title":"Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial","volume":"303","author":"Foell","year":"2010","journal-title":"JAMA"},{"key":"10.1136\/ard-2022-222553_bib24","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1007\/s10067-022-06165-4","article-title":"Use of MRP8\/14 in clinical practice as a predictor of outcome after methotrexate withdrawal in patients with juvenile idiopathic arthritis","volume":"41","author":"Sumner","year":"2022","journal-title":"Clin Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib25","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1136\/annrheumdis-2021-222029","article-title":"Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis: results from the PREVENT-JIA trial","volume":"81","author":"Gerss","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/ard-2022-222849","article-title":"Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial","volume":"82","author":"Brunner","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib27","author":"Clinicaltrials.gov"},{"key":"10.1136\/ard-2022-222553_bib28","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/art.23291","article-title":"Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers","volume":"58","author":"Nistala","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib29","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.3899\/jrheum.081179","article-title":"Th1 and Th17 predominance in the Enthesitis-related arthritis form of juvenile idiopathic arthritis","volume":"36","author":"Mahendra","year":"2009","journal-title":"J Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib30","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1093\/rheumatology\/kes162","article-title":"Th1 and Th17 cell subpopulations are enriched in the peripheral blood of patients with systemic juvenile idiopathic arthritis","volume":"51","author":"Omoyinmi","year":"2012","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib31","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/art.40731","article-title":"Innate lymphoid cells and T cells contribute to the interleukin-17A signature detected in the synovial fluid of patients with juvenile idiopathic arthritis","volume":"71","author":"Rosser","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib32","doi-asserted-by":"crossref","first-page":"848168","DOI":"10.3389\/fimmu.2022.848168","article-title":"Increased development of Th1, Th17, and Th1.17 cells under T1 polarizing conditions in juvenile idiopathic arthritis","volume":"13","author":"Patrick","year":"2022","journal-title":"Front Immunol"},{"key":"10.1136\/ard-2022-222553_bib33","doi-asserted-by":"crossref","first-page":"14751","DOI":"10.1073\/pnas.1003852107","article-title":"Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment","volume":"107","author":"Nistala","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1136\/ard-2022-222553_bib34","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1002\/art.30332","article-title":"Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis","volume":"63","author":"Cosmi","year":"2011","journal-title":"Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib35","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1002\/art.38647","article-title":"T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity","volume":"66","author":"Piper","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib36","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41584-020-0491-4","article-title":"Transforming clinical trials in rheumatology: towards patient-centric precision medicine","volume":"16","author":"Pitzalis","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib37","doi-asserted-by":"crossref","first-page":"213028","DOI":"10.1136\/annrheumdis-2018-213030","article-title":"Treating juvenile idiopathic arthritis to target: recommendations of an international task force","volume":"77","author":"Ravelli","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib38","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/ard.2007.073445","article-title":"The magnitude of early response to methotrexate therapy predicts long-term outcome of patients with juvenile idiopathic arthritis","volume":"67","author":"Bartoli","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib39","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/rheumatology\/kep352","article-title":"Disease activity and disability in children with juvenile idiopathic arthritis one year following presentation to paediatric rheumatology. Results from the childhood arthritis prospective study","volume":"49","author":"Hyrich","year":"2010","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib40","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1002\/art.40519","article-title":"Long-term outcomes following achievement of clinically inactive disease in juvenile idiopathic arthritis: the importance of definition","volume":"70","author":"Shoop-Worrall","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/acr.23853","article-title":"Long-term outcomes in juvenile idiopathic arthritis: eighteen years of follow\u2010up in the population\u2010based Nordic juvenile idiopathic arthritis cohort","volume":"72","author":"Glerup","year":"2020","journal-title":"Arthritis Care Res"},{"key":"10.1136\/ard-2022-222553_bib42","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1136\/annrheumdis-2016-210511","article-title":"How common is clinically inactive disease in a prospective cohort of patients with juvenile idiopathic arthritis? the importance of definition","volume":"76","author":"Shoop-Worrall","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib43","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1136\/annrheumdis-2014-207164","article-title":"The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort","volume":"75","author":"Guzman","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib44","first-page":"2290","article-title":"Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis","volume":"31","author":"Wallace","year":"2004","journal-title":"J Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib45","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/S2665-9913(20)30025-4","article-title":"Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study","volume":"2","author":"Kearsley-Fleet","year":"2020","journal-title":"Lancet Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib46","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/art.41390","article-title":"New medications are needed for children with juvenile idiopathic arthritis","volume":"72","author":"Brunner","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib47","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nrrheum.2014.212","article-title":"Management of juvenile idiopathic arthritis: hitting the target","volume":"11","author":"Hinze","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s41927-021-00192-5","article-title":"Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential","volume":"5","author":"Grayling","year":"2021","journal-title":"BMC Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib49","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nrrheum.2016.156","article-title":"Enhancing translational research in paediatric rheumatology through standardization","volume":"12","author":"Yeung","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib50","doi-asserted-by":"crossref","first-page":"160018","DOI":"10.1038\/sdata.2016.18","article-title":"The fair guiding principles for scientific data management and stewardship","volume":"3","author":"Wilkinson","year":"2016","journal-title":"Sci Data"},{"key":"10.1136\/ard-2022-222553_bib51","doi-asserted-by":"crossref","DOI":"10.1093\/rheumatology\/keac132.019","article-title":"OA19 Successes and challenges in harmonising four national juvenile idiopathic arthritis cohorts: an example from CLUSTER consortium","volume":"61","author":"Lawson-Tovey","year":"2022","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib52","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1136\/annrheumdis-2017-212141","article-title":"Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research","volume":"77","author":"McCann","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/rheumatology\/kez214","article-title":"CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis","volume":"59","author":"McErlane","year":"2020","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib54","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1002\/art.41888","article-title":"Optimizing the start time of biologics in polyarticular juvenile idiopathic arthritis: a comparative effectiveness study of childhood arthritis and rheumatology research alliance consensus treatment plans","volume":"73","author":"Kimura","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib55","doi-asserted-by":"crossref","first-page":"e0182751","DOI":"10.1371\/journal.pone.0182751","article-title":"Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis","volume":"12","author":"Choi","year":"2017","journal-title":"PLoS One"},{"key":"10.1136\/ard-2022-222553_bib56","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.medj.2022.05.002","article-title":"Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases","volume":"3","author":"Korsunsky","year":"2022","journal-title":"Med"},{"key":"10.1136\/ard-2022-222553_bib57","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41584-022-00790-8","article-title":"Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission","volume":"18","author":"Kurowska-Stolarska","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41385-021-00456-w","article-title":"The fellowship of regulatory and tissue-resident memory cells","volume":"15","author":"Barros","year":"2022","journal-title":"Mucosal Immunol"},{"key":"10.1136\/ard-2022-222553_bib59","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/art.27284","article-title":"Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression","volume":"62","author":"Hunter","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib60","doi-asserted-by":"crossref","first-page":"6435","DOI":"10.4049\/jimmunol.172.10.6435","article-title":"CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis","volume":"172","author":"de Kleer","year":"2004","journal-title":"J Immunol"},{"key":"10.1136\/ard-2022-222553_bib61","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4049\/jimmunol.0803474","article-title":"High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population","volume":"185","author":"Moncrieffe","year":"2010","journal-title":"J Immunol"},{"key":"10.1136\/ard-2022-222553_bib62","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1182\/blood-2012-08-443473","article-title":"CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines","volume":"121","author":"Pesenacker","year":"2013","journal-title":"Blood"},{"key":"10.1136\/ard-2022-222553_bib63","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1136\/annrheumdis-2014-206226","article-title":"A circulating reservoir of pathogenic-like CD4+ T cells shares a genetic and phenotypic signature with the inflamed synovial micro-environment","volume":"75","author":"Spreafico","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib64","doi-asserted-by":"crossref","first-page":"e149185","DOI":"10.1172\/jci.insight.149185","article-title":"Th1 polarization defines the synovial fluid T cell compartment in oligoarticular juvenile idiopathic arthritis","volume":"6","author":"Jul\u00e9","year":"2021","journal-title":"JCI Insight"},{"key":"10.1136\/ard-2022-222553_bib65","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1038\/s41467-021-22975-7","article-title":"Conserved human effector treg cell transcriptomic and epigenetic signature in arthritic joint inflammation","volume":"12","author":"Mijnheer","year":"2021","journal-title":"Nat Commun"},{"key":"10.1136\/ard-2022-222553_bib66","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13075-022-02913-8","article-title":"Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype","volume":"24","author":"Simonds","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"10.1136\/ard-2022-222553_bib67","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41584-020-00570-2","article-title":"Location, location, location: how the tissue microenvironment affects inflammation in RA","volume":"17","author":"Buckley","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib68","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41577-021-00540-z","article-title":"Fibroblasts as immune regulators in infection, inflammation and cancer","volume":"21","author":"Davidson","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"10.1136\/ard-2022-222553_bib69","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-021-03634-9","article-title":"Exploring tissue architecture using spatial transcriptomics","volume":"596","author":"Rao","year":"2021","journal-title":"Nature"},{"key":"10.1136\/ard-2022-222553_bib70","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13073-022-01075-1","article-title":"An introduction to spatial transcriptomics for biomedical research","volume":"14","author":"Williams","year":"2022","journal-title":"Genome Med"},{"key":"10.1136\/ard-2022-222553_bib71","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.tig.2022.01.004","article-title":"A decade of molecular cell atlases","volume":"38","author":"Quake","year":"2022","journal-title":"Trends Genet"},{"key":"10.1136\/ard-2022-222553_bib72","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","article-title":"Locally renewing resident synovial macrophages provide a protective barrier for the joint","volume":"572","author":"Culemann","year":"2019","journal-title":"Nature"},{"key":"10.1136\/ard-2022-222553_bib73","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41586-019-1263-7","article-title":"Distinct fibroblast subsets drive inflammation and damage in arthritis","volume":"570","author":"Croft","year":"2019","journal-title":"Nature"},{"key":"10.1136\/ard-2022-222553_bib74","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/s41591-020-0939-8","article-title":"Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis","volume":"26","author":"Alivernini","year":"2020","journal-title":"Nat Med"},{"key":"10.1136\/ard-2022-222553_bib75","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.celrep.2019.07.091","article-title":"Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes","volume":"28","author":"Lewis","year":"2019","journal-title":"Cell Rep"},{"key":"10.1136\/ard-2022-222553_bib76","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/annrheumdis-2018-214539","article-title":"Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients","volume":"78","author":"Humby","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"10.1136\/ard-2022-222553_bib77","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0140-6736(20)32341-2","article-title":"Rituximab versus tocilizumab in anti-TNF inadequate Responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial","volume":"397","author":"Humby","year":"2021","journal-title":"Lancet"},{"key":"10.1136\/ard-2022-222553_bib78","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41591-022-01789-0","article-title":"Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial","volume":"28","author":"Rivellese","year":"2022","journal-title":"Nat Med"},{"key":"10.1136\/ard-2022-222553_bib79","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat Immunol"},{"key":"10.1136\/ard-2022-222553_bib80","article-title":"Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis","author":"Zhang","year":"2022","journal-title":"BioRxiv"},{"key":"10.1136\/ard-2022-222553_bib81","first-page":"P005","article-title":"Feasibility study of taking minimally invasive ultrasound-guided tissue biopsies of synovial tissue in children with juvenile idiopathic arthritis for research","volume":"20","author":"Bolton","year":"2022","journal-title":"Pediatric Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib82","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1002\/art.22122","article-title":"Pediatric granulomatous arthritis: an international registry","volume":"54","author":"Ros\u00e9","year":"2006","journal-title":"Arthritis Rheum"},{"key":"10.1136\/ard-2022-222553_bib83","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.4049\/jimmunol.1700507","article-title":"Nod2 deficiency augments Th17 responses and exacerbates autoimmune arthritis","volume":"201","author":"Napier","year":"2018","journal-title":"J Immunol"},{"key":"10.1136\/ard-2022-222553_bib84","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/08923973.2018.1510963","article-title":"Increased inflammatory responsiveness of peripheral blood mononuclear cells (PBMCs) to in vitro NOD2 ligand stimulation in patients with ankylosing spondylitis","volume":"40","author":"Vanaki","year":"2018","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"10.1136\/ard-2022-222553_bib85","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1038\/s41467-020-18961-0","article-title":"T cell-intrinsic role for NOD2 in protection against TH17-mediated uveitis","volume":"11","author":"Napier","year":"2020","journal-title":"Nat Commun"},{"key":"10.1136\/ard-2022-222553_bib86","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20201006","article-title":"LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages","volume":"218","author":"Omarjee","year":"2021","journal-title":"J Exp Med"},{"key":"10.1136\/ard-2022-222553_bib87","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41586-022-05111-3","article-title":"LACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages","volume":"609","author":"Wei","year":"2022","journal-title":"Nature"},{"key":"10.1136\/ard-2022-222553_bib88","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1002\/art.41043","article-title":"Toward accelerated authorization and access to new medicines for juvenile idiopathic arthritis","volume":"71","author":"Schanberg","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"10.1136\/ard-2022-222553_bib89","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1186\/s13063-021-05651-5","volume":"22","author":"Ramanan","year":"2021","journal-title":"Trials"},{"key":"10.1136\/ard-2022-222553_bib90","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1016\/S1470-2045(15)00396-4","article-title":"Research methods to change clinical practice for patients with rare cancers","volume":"17","author":"Billingham","year":"2016","journal-title":"Lancet Oncol"},{"issue":"Suppl 1","key":"10.1136\/ard-2022-222553_bib91","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1097\/QAI.0000000000001748","article-title":"Optimizing clinical trial design to maximize evidence generation in pediatric HIV","volume":"78","author":"Ford","year":"2018","journal-title":"J Acquir Immune Defic Syndr"},{"key":"10.1136\/ard-2022-222553_bib92","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1093\/rheumatology\/keac128","article-title":"The neglected\u2002and untreated pains of CRMO and SAPHO syndrome","volume":"61","author":"Sinnappurajar","year":"2022","journal-title":"Rheumatology"},{"key":"10.1136\/ard-2022-222553_bib93","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1002\/art.41730","article-title":"Mycophenolate mofetil versus cyclophosphamide for remission induction in childhood polyarteritis nodosa: an open-label, randomized, Bayesian Noninferiority trial","volume":"73","author":"Brogan","year":"2021","journal-title":"Arthritis Rheumatol"}],"container-title":["Annals of the Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003496724004308?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003496724004308?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/ard-2022-222553","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:01Z","timestamp":1739503201000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003496724004308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":93,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["S0003496724004308"],"URL":"https:\/\/doi.org\/10.1136\/ard-2022-222553","relation":{},"ISSN":["0003-4967"],"issn-type":[{"value":"0003-4967","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis","name":"articletitle","label":"Article Title"},{"value":"Annals of the Rheumatic Diseases","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1136\/ard-2022-222553","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2023 \u00a9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by Elsevier Inc. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}