{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:34:28Z","timestamp":1770687268076,"version":"3.49.0"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ek0410025h"],"award-info":[{"award-number":["18ek0410025h"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteopontin (OPN) was initially described as a protein involved in bone metabolism, but the roles played by OPN in the immune system and allergic reactions have attracted increasing attention. Here, we clarify the OPN\u2010related dynamics of severe cutaneous adverse drug reactions, and assess whether the OPN level has utility for classifying such reactions and serving as a biomarker of severity. Serum OPN levels in patients with drug\u2010induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms (DIHS\/DRESS), Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN) and erythema multiforme\u2010type drug reaction (EM\u2010DR) were quantified by ELISA. The OPN sources were analyzed by dual immunofluorescence assay of DIHS, SJS\/TEN and EM\u2010DR biopsy specimens. The serum OPN levels of DIHS\/DRESS patients (489.1\u2009\u00b1\u200937.0\u00a0ng\/mL) and SJS\/TEN patients (508.5\u2009\u00b1\u200947.8\u00a0ng\/mL) were significantly higher compared with controls (314.4\u2009\u00b1\u200914.3\u00a0ng\/mL; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). After treatment, the serum OPN level of DIHS\/DRESS patients decreased to that of controls. In addition, OPN levels in DIHS\/DRESS patients and SJS\/TEN patients were higher than in patients with EM\u2010DR (Mann\u2013Whitney U test, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). However, when the Kruskal\u2013Wallis test was used to compare the OPN levels among the three groups of patients, the difference was not significant (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.055). Dual immunofluorescence assay revealed that T lymphocytes and macrophages were the main OPN sources in DIHS, SJS\/TEN and EM\u2010DR patients. These data suggest that the OPN level can be used to evaluate the severity of inflammation in patients experiencing drug reactions.<\/jats:p>","DOI":"10.1111\/1346-8138.16670","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:21:25Z","timestamp":1671603685000},"page":"536-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated serum osteopontin levels in patients with severe cutaneous adverse drug reactions"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-1950","authenticated-orcid":false,"given":"Marie","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Dermatology Showa University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Koshikawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Showa University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-5167","authenticated-orcid":false,"given":"Hideaki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Dermatology Showa University, School of Medicine  Tokyo Japan"},{"name":"Department of Dermatology Showa University Northern Yokohama Hospital  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-9824","authenticated-orcid":false,"given":"Naoko","family":"Inomata","sequence":"additional","affiliation":[{"name":"Department of Dermatology Showa University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0297-6627","authenticated-orcid":false,"given":"Yukie","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Environmental Immuno\u2010Dermatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Aihara","sequence":"additional","affiliation":[{"name":"Department of Environmental Immuno\u2010Dermatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-7211","authenticated-orcid":false,"given":"Hirohiko","family":"Sueki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Showa University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.7.15.8262332"},{"key":"e_1_2_7_3_1","first-page":"2061","article-title":"Enhanced local production of osteopontin in rheumatoid joints","volume":"29","author":"Ohshima S","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1580"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2010.03549.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2014.2477"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.08.052"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2015-0821"},{"key":"e_1_2_7_9_1","first-page":"225","article-title":"Molecular and cellular basis of genetic resistance to bacterial infection. The role of the early T\u2010lymphocyte activation\u20101\/osteopontin gene","volume":"13","author":"Patarca R","year":"1993","journal-title":"Crit Rev Immunol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.9.1219"},{"key":"e_1_2_7_11_1","first-page":"1523","article-title":"Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti\u2010DNA autoantibodies","volume":"78","author":"Iizuka J","year":"1998","journal-title":"Lab Invest"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.860"},{"key":"e_1_2_7_13_1","first-page":"148","article-title":"Osteopontin contributes TH2 immune responses: spontaneous development of atopic dermatitis like lesion and enhanced asthma\u2010like response","volume":"42","author":"Katagiri K","year":"2006","journal-title":"J Dermatol Sci"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000100880"},{"key":"e_1_2_7_15_1","first-page":"79","article-title":"Osteopontin expression in chronic plaque psoriasis: an association with the severity of disease","volume":"34","author":"Abdou AG","year":"2012","journal-title":"Anal Quant Cytol Histol"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0394632015592101"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16670","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.16670","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16670","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T02:02:50Z","timestamp":1692669770000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.16670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/1346-8138.16670"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.16670","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"2022-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}