{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:41:56Z","timestamp":1783528916629,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Maire Lisko Foundation"},{"DOI":"10.13039\/501100018949","name":"Oulu University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We aimed to study intestinal immune activation status in juvenile idiopathic arthritis (JIA) by assessing intestinal human leucocyte antigen (HLA) class II expression and the mRNA expression levels of the pro- and anti-inflammatory mediators and pattern recognition receptors. HLA-D-related (HLA-DR) expression was assessed using immunohistochemical staining of frozen sections in 11 children with JIA and 17 controls. The gene expression levels of the anti- and proinflammatory cytokines, lymphocyte recognition receptors and pattern recognition receptors were studied with reverse transcription\u2013polymerase chain reaction (RT\u2013PCR) in 14 children with JIA and 12 controls. All subjects had various gastrointestinal (GI) symptoms indicating endoscopic examinations, but eventually were not diagnosed with GI disease. In JIA patients, the expression of HLA-DR was increased in the crypt epithelial cells and in the epithelial basement membrane of the ileum when compared with the controls. Positive HLA-DR staining in the ileal mucosa was associated with the presence of high clinical disease activity of JIA and low mRNA expression of anti-inflammatory mediators, such as forkhead box protein P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and transforming growth factor (TGF)-beta. Low ileal expression of interleukin (IL)-10, TGF-\u03b2, FoxP3, Toll-like receptor 2 (TLR-2) and TLR-4 transcripts correlated significantly with a high clinical disease activity in the JIA patients. The increased HLA-DR expression suggests enhanced intestinal antigen presentation in JIA. A correlation between clinical disease activity and low gene expression of tolerogenic mediators in the ileum supports the hypothesis that a link exists between the gut immune system and JIA.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04663.x","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T11:51:07Z","timestamp":1345549867000},"page":"266-273","source":"Crossref","is-referenced-by-count":18,"title":["Altered expression of intestinal human leucocyte antigen D-related and immune signalling molecules in juvenile idiopathic arthritis"],"prefix":"10.1093","volume":"170","author":[{"given":"M","family":"Arvonen","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Oulu, Oulu University Hospital, Oulu"},{"name":"Department of Pathology, University of Oulu, Oulu University Hospital, Oulu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"V\u00e4h\u00e4salo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oulu, Oulu University Hospital, Oulu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Turunen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oulu, Oulu University Hospital, Oulu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H M","family":"Salo","sequence":"additional","affiliation":[{"name":"Immune Response Unit, National Institute for Health and Welfare, Helsinki"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"M\u00e4ki","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, University of Tampere, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Laurila","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, University of Tampere, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Vaarala","sequence":"additional","affiliation":[{"name":"Immune Response Unit, National Institute for Health and Welfare, Helsinki"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T J","family":"Karttunen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oulu, Oulu University Hospital, Oulu"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"2021122708261081900_cei4663-bib-0001","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.2337\/db08-0331","article-title":"The \u2018perfect storm\u2019 for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity","volume":"57","author":"Vaarala","year":"2008","journal-title":"Diabetes"},{"key":"2021122708261081900_cei4663-bib-0002","first-page":"1567","article-title":"Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy \u2013 a prospective study","volume":"20","author":"Mielants","year":"1993","journal-title":"J Rheumatol"},{"key":"2021122708261081900_cei4663-bib-0003","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1080\/03009740701394005","article-title":"Intestinal immune activation in juvenile idiopathic arthritis and connective tissue disease","volume":"36","author":"Kokkonen","year":"2007","journal-title":"Scand J Rheumatol"},{"key":"2021122708261081900_cei4663-bib-0004","first-page":"128","article-title":"Increase of duodenal and ileal mucosal cytotoxic lymphocytes in juvenile idiopathic arthritis","volume":"28","author":"Arvonen","year":"2010","journal-title":"Clin Exp Rheumatol"},{"key":"2021122708261081900_cei4663-bib-0005","first-page":"773","article-title":"Increased gut permeability in juvenile chronic arthritides. 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