{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:26:53Z","timestamp":1793910413435,"version":"4.8.0"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":88,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labor, and Welfare of Japan (Health and Labor Sciences Research Grant for Research on Development of New Drugs H24-bio-ippan-002)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether leucine\u2010rich \u03b1<jats:sub>2<\/jats:sub>\u2010glycoprotein (LRG) could be a biomarker for disease activity during interleukin\u20106 (IL\u20106) blockade treatment of rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme\u2010linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C\u2010reactive protein (CRP) and LRG were evaluated after treatment with anti\u2013IL\u20106 receptor antibody.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among tocilizumab\u2010treated RA patients, those with active disease (CDAI &gt;2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL\u20106 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL\u20106 blockade\u2013treated monkeys with low levels of CRP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Under conditions of IL\u20106 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL\u20106 blockade treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39164","type":"journal-article","created":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T12:20:44Z","timestamp":1430137244000},"page":"2056-2060","source":"Crossref","is-referenced-by-count":80,"title":["Brief Report: Leucine\u2010Rich \u03b1<sub>2<\/sub>\u2010Glycoprotein as a Potential Biomarker for Joint Inflammation During Anti\u2013Interleukin\u20106 Biologic Therapy in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Minoru","family":"Fujimoto","sequence":"first","affiliation":[{"name":"National Institute of Biomedical Innovation Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Serada","sequence":"additional","affiliation":[{"name":"National Institute of Biomedical Innovation Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ogata","sequence":"additional","affiliation":[{"name":"Osaka University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Nanki","sequence":"additional","affiliation":[{"name":"Tokyo Medical and Dental University and Teikyo University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Hattori","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Gotemba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kohsaka","sequence":"additional","affiliation":[{"name":"Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Miyasaka","sequence":"additional","affiliation":[{"name":"Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Naka","sequence":"additional","affiliation":[{"name":"National Institute of Biomedical Innovation Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"e_1_2_8_2_1","article-title":"Targeting of interleukin\u20106 for the treatment of rheumatoid arthritis: a review and update","author":"Tanaka T","year":"2013","journal-title":"Rheumatology (Sunnyvale)"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902113400607"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204573"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.118919"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.22936"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.104"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30129"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086184"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.31.1159"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1691"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2008.03.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199807)41:7<1203::AID-ART9>3.0.CO;2-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12345"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203158"}],"container-title":["Arthritis &amp; 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