{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:33:06Z","timestamp":1787117586243,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"Objective<\/jats:title>Juvenile idiopathic arthritis (JIA<\/jats:styled-content>) is the most common inflammatory arthritis in children; however, an aggressive, erosive\u00a0arthritis of little\u2010known immunologic mechanism occurs 20 times more frequently in children with Down syndrome. This study was undertaken to characterize T cell and B cell polyreactivity, follicular helper T (Tfh) cell, peripheral helper T (Tph) cell, and Treg cell responses, and synovial inflammation in Down syndrome\u2013associated arthritis (DA<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Multiparametric flow cytometric analysis and Simplified Presentation of Incredibly Complex Evaluations (SPICE<\/jats:styled-content>) software were used to examine peripheral blood B cell populations and T cell cytokine responses in patients with DA<\/jats:styled-content>, JIA<\/jats:styled-content>, Down syndrome (trisomy 21 [T21]), and in healthy controls. Tfh and Tph cell frequency and origin, in addition to Treg cell frequency, were also evaluated. Synovial inflammation was assessed by immunohistology.<\/jats:p><\/jats:sec>Results<\/jats:title>Expansion of IgM\u2010only memory B cells was demonstrated in DA<\/jats:styled-content> compared to JIA<\/jats:styled-content> (mean \u00b1 SEM<\/jats:styled-content> 22.48 \u00b1 3.278 versus 9.011 \u00b1 1.317; P<\/jats:italic> = 0.005), paralleled by decreased frequency of transitional B cells. T cell responses in DA<\/jats:styled-content> were characterized by marked functional plasticity, as was evident from the increased frequency of polyfunctional CD<\/jats:styled-content>8+ Th cells (P<\/jats:italic> < 0.05), CD<\/jats:styled-content>161+ Th cells (P<\/jats:italic> < 0.05), and CD<\/jats:styled-content>8\u2212 Th cells (P<\/jats:italic> < 0.001), and positivity for tumor necrosis factor, interferon\u2010\u03b3, interleukin\u201017A, or granulocyte\u2013macrophage colony\u2010stimulating factor, compared to all other groups. Significant expansion of CXCR<\/jats:styled-content>3+CCR<\/jats:styled-content>6+ (Th1\/Th17) Tfh cells (P<\/jats:italic> = 0.003) and CXCR<\/jats:styled-content>3+CCR<\/jats:styled-content>6+ Tph cells (P<\/jats:italic> = 0.01), paralleled by a decrease in CXCR<\/jats:styled-content>3\u2212CCR<\/jats:styled-content>6\u2212 (Th2) Tfh cells was observed in DA<\/jats:styled-content> compared to T21. Treg cells were significantly reduced in DA<\/jats:styled-content> compared to T21 (mean \u00b1 SEM<\/jats:styled-content> 7.111 \u00b1 0.9518 versus 11.96 \u00b1 1.055 versus; P<\/jats:italic> = 0.0028), with a specific reduction in the naive:memory Treg cell ratio. Marked synovial tissue inflammation and increased T cell and B cell infiltrations were demonstrated in DA<\/jats:styled-content> compared to JIA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>DA<\/jats:styled-content> is more common and more aggressive than JIA<\/jats:styled-content>. It is characterized by increased polyreactive Th, Tfh, and Tph cell responses, reduced Treg cell frequency, and evidence of increased synovial inflammation, all of which are potentially distinct from JIA<\/jats:styled-content> and T21.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41150","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T02:40:14Z","timestamp":1572230414000},"page":"677-686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Increased T Cell Plasticity With Dysregulation of Follicular Helper T, Peripheral Helper T, and Treg Cell Responses in Children With Juvenile Idiopathic Arthritis and Down Syndrome\u2013Associated Arthritis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-694X","authenticated-orcid":false,"given":"C.","family":"Foley","sequence":"first","affiliation":[{"name":"Our Lady\u2019s Children\u2019s Hospital Crumlin and Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Floudas","sequence":"additional","affiliation":[{"name":"Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Canavan","sequence":"additional","affiliation":[{"name":"Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Biniecka","sequence":"additional","affiliation":[{"name":"Centre for Arthritis and Rheumatic Diseases EULAR Centre of Excellence St. Vincent\u2019s University Hospital, and University College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"MacDermott","sequence":"additional","affiliation":[{"name":"Our Lady\u2019s Children\u2019s Hospital Crumlin, Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Veale","sequence":"additional","affiliation":[{"name":"Centre for Arthritis and Rheumatic Diseases EULAR Centre of Excellence St. Vincent\u2019s University Hospital, and University College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-3680","authenticated-orcid":false,"given":"R. H.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Tallaght University Hospital and Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. 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