{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:09:25Z","timestamp":1780733365205,"version":"3.54.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K08405"],"award-info":[{"award-number":["18K08405"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines\/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines\/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines\/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant\/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0252116","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:29:00Z","timestamp":1621603740000},"page":"e0252116","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines\/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis"],"prefix":"10.1371","volume":"16","author":[{"given":"Manami","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0574-9611","authenticated-orcid":true,"given":"Kei","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Suga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadamichi","family":"Kasuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-923X","authenticated-orcid":true,"given":"Hiroki","family":"Furuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arifumi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Furuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiryo","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"issue":"9","key":"pone.0252116.ref001","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"D Aletaha","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"11","key":"pone.0252116.ref002","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1136\/ard.2011.151316","article-title":"Tenosynovitis of the extensor carpi ulnaris tendon predicts erosive progression in early rheumatoid arthritis","volume":"70","author":"S Lillegraven","year":"2011","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"pone.0252116.ref003","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1136\/annrheumdis-2015-208138","article-title":"van der Helm-van Mil AH. 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Preliminary definition of improvement in rheumatoid arthritis","volume":"38","author":"DT Felson","year":"1995","journal-title":"Arthritis Rheum"},{"key":"pone.0252116.ref040","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"L. Breiman","year":"2001","journal-title":"Mach Learn"},{"key":"pone.0252116.ref041","first-page":"113","article-title":"Unsupervised learning with random forest predictors","volume":"15","author":"T Shi","year":"2006","journal-title":"J Comput Graph Stat"},{"key":"pone.0252116.ref042","first-page":"1802.03426","article-title":"Uniform Manifold Approximation and Projection for Dimension Reduction","author":"L McInnes","year":"2018","journal-title":"ArXiv"},{"key":"pone.0252116.ref043","unstructured":"Kaufman L, Rousseeuw PJ. Clustering by means of medoids. In: Dodge Y, editor. Statistical Data Analysis based on the L1 Norm. North-Holland, Amsterdam1987. p. 405\u201316."},{"issue":"6","key":"pone.0252116.ref044","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/ard.2010.147272","article-title":"Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level","volume":"70","author":"M Gutierrez","year":"2011","journal-title":"Ann Rheum Dis"},{"issue":"7","key":"pone.0252116.ref045","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11926-019-0834-9","article-title":"ILC3 in Axial Spondyloarthritis: the Gut Angle","volume":"21","author":"D Mauro","year":"2019","journal-title":"Curr Rheumatol Rep"},{"issue":"8","key":"pone.0252116.ref046","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00296-016-3480-9","article-title":"Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials","volume":"36","author":"S Kunwar","year":"2016","journal-title":"Rheumatology international"},{"issue":"5","key":"pone.0252116.ref047","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/annrheumdis-2016-209831","article-title":"A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate","volume":"76","author":"JS Smolen","year":"2017","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"pone.0252116.ref048","doi-asserted-by":"crossref","first-page":"e4725","DOI":"10.1371\/journal.pone.0004725","article-title":"Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin","volume":"4","author":"PA Jansen","year":"2009","journal-title":"PLoS One"},{"issue":"8","key":"pone.0252116.ref049","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/rheumatology\/kes001","article-title":"A randomized placebo-controlled trial of methotrexate in psoriatic arthritis","volume":"51","author":"GH Kingsley","year":"2012","journal-title":"Rheumatology (Oxford)"},{"issue":"7","key":"pone.0252116.ref050","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1002\/art.40851","article-title":"Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial","volume":"71","author":"PJ Mease","year":"2019","journal-title":"Arthritis Rheumatol."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:29:45Z","timestamp":1621603785000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252116"}},"subtitle":[],"editor":[{"given":"Gordana","family":"Ivanac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0252116","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-105953\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-105953\/v1","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]}}}