{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:59:29Z","timestamp":1785599969579,"version":"3.56.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chong Kun Dang Pharmaceutical Corporation","award":["800-20150258"],"award-info":[{"award-number":["800-20150258"]}]},{"name":"Chong Kun Dang Pharmaceutical Corporation","award":["02-2015-048"],"award-info":[{"award-number":["02-2015-048"]}]},{"name":"SNUBH Research Fund","award":["800-20150258"],"award-info":[{"award-number":["800-20150258"]}]},{"name":"SNUBH Research Fund","award":["02-2015-048"],"award-info":[{"award-number":["02-2015-048"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Disease Markers"],"published-print":{"date-parts":[[2018,11,14]]},"abstract":"<jats:p>Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-)<jats:italic>\u03b1<\/jats:italic>, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>) and IL-6 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.007<\/mml:mn><\/mml:math>) and TNF-<jats:italic>\u03b1<\/jats:italic>(<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28&gt;\u20093.2 and with DAS28\u2009\u2264\u20093.2, RA patients with radiographic progression (\u0394SHS change\/year\u2009\u2265\u20091) had significantly higher baseline levels of Sema4D than those without progression (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.029<\/mml:mn><\/mml:math>). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.045<\/mml:mn><\/mml:math>). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.<\/jats:p>","DOI":"10.1155\/2018\/2318386","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T23:30:38Z","timestamp":1542238238000},"page":"1-10","source":"Crossref","is-referenced-by-count":14,"title":["Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6107-9523","authenticated-orcid":true,"given":"You-Jung","family":"Ha","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyoun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Wan","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-1159","authenticated-orcid":true,"given":"Eun Ha","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-3437","authenticated-orcid":true,"given":"Yeong Wook","family":"Song","sequence":"additional","affiliation":[{"name":"WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-8611","authenticated-orcid":true,"given":"Yun Jong","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea"},{"name":"Department of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21405"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00872-5"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21984"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.057497"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.092254"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.2.122"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0652-z"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90625-Z"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.201"},{"issue":"2","key":"11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4049\/jimmunol.148.2.318","volume":"148","year":"1992","journal-title":"Journal of Immunology"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxg098"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.3.1175"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1885"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2445"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1002\/art.39086"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-40"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19915"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903527"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/nature11000"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2489"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"issue":"3","key":"24","first-page":"743","volume":"26","year":"1999","journal-title":"The Journal of Rheumatology"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1002\/art.30163"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125860"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4895050"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090533"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1186\/ar3380"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1186\/ar2165"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2653"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1038\/nm1538"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.132852"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.035691"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.068247"},{"issue":"7","key":"36","first-page":"1277","volume":"35","year":"2008","journal-title":"The Journal of Rheumatology"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.152074"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2011.02.011"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-012-2397-1"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-014-3056-5"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.121764"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1038\/srep18421"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0740-0"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker129"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00063-7"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00322"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1002\/art.39837"},{"issue":"9","key":"48","first-page":"16352","volume":"8","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12275"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.09.009"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1186\/ar3881"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4070-x"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.05.010"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2017.07.001"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1443"}],"container-title":["Disease Markers"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/dm\/2018\/2318386.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/dm\/2018\/2318386.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/dm\/2018\/2318386.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T03:14:47Z","timestamp":1694056487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/dm\/2018\/2318386\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":55,"alternative-id":["2318386","2318386"],"URL":"https:\/\/doi.org\/10.1155\/2018\/2318386","relation":{},"ISSN":["0278-0240","1875-8630"],"issn-type":[{"value":"0278-0240","type":"print"},{"value":"1875-8630","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]}}}