{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:02:22Z","timestamp":1790179342200,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08\u2010AR072075"],"award-info":[{"award-number":["K08\u2010AR072075"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["448863690"],"award-info":[{"award-number":["448863690"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Canakinumab is a human anti\u2013interleukin\u20101\u03b2 (anti\u2013IL\u20101\u03b2) blocking agent that effectively neutralizes IL\u20101\u03b2\u2013mediated signaling for treatment of systemic juvenile idiopathic arthritis (JIA). While many patients have dramatic clinical response to IL\u20101 blockade, approximately one\u2010third fail to respond, but there are currently no validated clinical or immunologic predictors of response. We undertook this study to characterize distinct gene signatures for treatment response and nonresponse to canakinumab in systemic JIA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a secondary analysis of whole\u2010blood gene expression microarrays using blood samples obtained from healthy controls and systemic JIA patients at baseline and on day 3 after canakinumab treatment (GEO accession no. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE80060\">GSE80060<\/jats:ext-link>). Patients were considered strong clinical responders if they met the ACR90 response (exhibited \u226590% improvement in the American College of Rheumatology [ACR] JIA response criteria; nonresponders were those who met ACR30 [exhibiting \u226430% improvement in the ACR JIA response criteria]). A random\u2010effects model with patient identity as the random variable was used for differential expression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a distinct gene expression signature in patients with a strong clinical response to canakinumab treatment as compared to nonresponders, mediated by up\u2010regulation of neutrophil\u2010 and IL\u20101\u2013associated genes and characterized by increasing divergence from control transcriptomes with increasing clinical response. We also identified a signature including up\u2010regulated <jats:italic>CD163<\/jats:italic> expression that was associated with canakinumab nonresponse. Intriguingly, canakinumab treatment induced either up\u2010 or down\u2010regulation of type I interferon (IFN) genes, independent of clinical response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here, we identify a gene signature in systemic JIA patients prior to receiving treatment that distinguishes strong responders to canakinumab from nonresponders. Further prospective studies are needed to assess the utility of these insights for treatment decisions in systemic JIA and to track the association of up\u2010regulated type I IFN signatures with systemic JIA complications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41640","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T06:06:52Z","timestamp":1610777212000},"page":"1334-1340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Distinct Gene Expression Signatures Characterize Strong Clinical Responders Versus Nonresponders to Canakinumab in Children With Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-2148","authenticated-orcid":false,"given":"Emely L.","family":"Verweyen","sequence":"first","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Pickering","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei A.","family":"Grom","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-7051","authenticated-orcid":false,"given":"Grant S.","family":"Schulert","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.68"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.134254"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02995"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22644"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070070"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40865"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201903-0659OC"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-820852"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21889"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41073"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112802"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810787"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205099"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1212-x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20497"},{"key":"e_1_2_6_18_1","unstructured":"PickeringA.crossmeta: Cross platform meta\u2010analysis of microarray data. 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