{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:33:11Z","timestamp":1780471991821,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T00:00:00Z","timestamp":1235606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Fever of unknown origin is a diagnostic challenge in children, especially for differentiation of systemic\u2010onset juvenile idiopathic arthritis (systemic\u2010onset JIA) and infectious diseases. We undertook this study to analyze the relevance of myeloid\u2010related proteins (MRPs) 8 and 14, endogenous activators of Toll\u2010like receptor 4, in diagnosis and pathogenesis of systemic\u2010onset JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum concentrations of MRP\u20108\/MRP\u201014 were analyzed in 60 patients with systemic\u2010onset JIA, 85 patients with systemic infections, 40 patients with acute lymphoblastic leukemia, 5 patients with acute myeloblastic leukemia, 18 patients with neonatal\u2010onset multisystem inflammatory disease (NOMID), and 50 healthy controls. In addition, we investigated the link between interleukin\u20101\u03b2 (IL\u20101\u03b2) and MRP\u20108\/MRP\u201014 in systemic\u2010onset JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum MRP\u20108\/MRP\u201014 concentrations were significantly (<jats:italic>P<\/jats:italic> &lt; 0.001) elevated in patients with active systemic\u2010onset JIA (mean \u00b1 95% confidence interval 14,920 \u00b1 4,030 ng\/ml) compared with those in healthy controls (340 \u00b1 70 ng\/ml), patients with systemic infections (2,640 \u00b1 720 ng\/ml), patients with acute lymphoblastic leukemia (650 \u00b1 280 ng\/ml), patients with acute myeloblastic leukemia (840 \u00b1 940 ng\/ml), and patients with NOMID (2,830 \u00b1 580 ng\/ml). In contrast to C\u2010reactive protein levels, MRP\u20108\/MRP\u201014 concentrations distinguished systemic\u2010onset JIA from infections, with a specificity of 95%. MRP\u201014 in serum of patients with systemic\u2010onset JIA was a strong inducer of IL\u20101\u03b2 expression in phagocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The analysis of MRP\u20108\/MRP\u201014 in serum is an excellent tool for the diagnosis of systemic\u2010onset JIA, allowing early differentiation between patients with systemic\u2010onset JIA and those with other inflammatory diseases. MRP\u20108\/MRP\u201014 and IL\u20101\u03b2 represent a novel positive feedback mechanism activating phagocytes via 2 major signaling pathways of innate immunity during the pathogenesis of systemic\u2010onset JIA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24349","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T13:15:27Z","timestamp":1235654127000},"page":"883-891","source":"Crossref","is-referenced-by-count":171,"title":["The myeloid\u2010related proteins 8 and 14 complex, a novel ligand of toll\u2010like receptor 4, and interleukin\u20101\u03b2 form a positive feedback mechanism in systemic\u2010onset juvenile idiopathic arthritis"],"prefix":"10.1002","volume":"60","author":[{"given":"Michael","family":"Frosch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ahlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Wittkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Wulffraat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0084"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199809000-00011"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11530"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.14.9496"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00062-0"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20631"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2520"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.4049\/jimmunol.160.3.1427","article-title":"The human S100 protein MRP\u201014 is a novel activator of the \u03b22 integrin Mac\u20101 on neutrophils","volume":"160","author":"Newton RA","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1638"},{"key":"e_1_2_7_12_2","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.57.1.38"},{"issue":"9","key":"e_1_2_7_14_2","first-page":"S428","article-title":"Preliminary core set of outcome variables for use in JRA clinical trials","volume":"37","author":"Giannini EH","year":"1994","journal-title":"Arthritis Rheum"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371209"},{"key":"e_1_2_7_16_2","first-page":"2290","article-title":"Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis","volume":"31","author":"Wallace CA","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_17_2","first-page":"1058","article-title":"Preliminary definition of disease flare in juvenile rheumatoid arthritis","volume":"29","author":"Brunner HI","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11177"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10381"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)82399-6"},{"key":"e_1_2_7_22_2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1542\/peds.55.4.468","article-title":"Prolonged fever in children: review of 100 cases","volume":"55","author":"Pizzo PA","year":"1975","journal-title":"Pediatrics"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100670170100"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.061853"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01451062"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22981"},{"key":"e_1_2_7_27_2","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1182\/blood.V87.11.4824.bloodjournal87114824","article-title":"Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic\u2010onset juvenile chronic arthritis","volume":"87","author":"Cazzola M","year":"1996","journal-title":"Blood"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11683-7"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003163421103"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21061"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22841"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050640"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23437"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.076034"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1019"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22842"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200103)44:3<550::AID-ANR103>3.0.CO;2-5"},{"key":"e_1_2_7_38_2","first-page":"368","article-title":"Myeloid related proteins MRP8\/MRP14 may predict disease flares in juvenile idiopathic arthritis","volume":"22","author":"Schulze zur Wiesch A","year":"2004","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.005686"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1758"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10988"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1660"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.3.236"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0019-2805.2004.01836.x"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.24349","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.24349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T22:25:57Z","timestamp":1697063157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.24349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,26]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1002\/art.24349"],"URL":"https:\/\/doi.org\/10.1002\/art.24349","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,26]]}}}