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However, the exact pathophysiological mechanisms underlying the development of atherosclerosis remain unknown; currently, atherosclerosis is thought to involve an inflammatory process. Systemic inflammatory reactions and accumulation of immune cells in atherosclerotic lesions\n                    <jats:italic>in situ<\/jats:italic>\n                    are considered essential. We have comprehensively analyzed autoantibodies in patients with atherosclerosis by means of a newly developed high\u2010throughput autoantibody analysis system. A wide range of autoantibodies was found in sera from patients with atherosclerosis. After we statistically analyzed the titers of each autoantibody with conventional techniques, the results underwent text\u2010mining analyses based on natural language processing. Combinatory analysis revealed a close association between anti\u2010interleukin (IL)\u20105 antibody and atherosclerosis. Titers of anti\u2010IL\u20105 antibodies and serum IL\u20105 concentrations were also closely associated with other risk factors, such as low\u2010density lipoprotein cholesterol, serum creatinine, fasting plasma glucose, gender, and age, suggesting that suppressed IL\u20105 function mediated by autoantibodies in patients with atherosclerosis plays an important role in the disease process. To validate the clinical significance of these findings, we computed the specificity and sensitivity of titers of anti\u2010IL\u20105 autoantibodies for human atherosclerosis. When antibody titers of 1.49 were assumed to predict the presence of atherosclerosis, the sensitivity was 95.0% and the specificity 91.0%, with an area under the curve of 0.940. Our results provide important clues to understanding the role of autoantibody\u2010mediated immune reactions in human atherosclerosis and suggest novel therapeutic opportunities for management of the disease.\u2014Ishigami, T., Abe, K., Aoki, I., Minegishi, S., Ryo, A., Matsunaga, S., Matsuoka, K., Takeda, H., Sawasaki, T., Umemura, S., and Endo, Y., Anti\u2010interleukin\u20105 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin\u20105 levels. FASEB J. 27, 3437\u20133445 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-222653","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T08:44:27Z","timestamp":1369298667000},"page":"3437-3445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Anti\u2010interleukin\u20105 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin\u20105 levels"],"prefix":"10.1096","volume":"27","author":[{"given":"Tomoaki","family":"Ishigami","sequence":"first","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaito","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shintaro","family":"Minegishi","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihide","family":"Ryo","sequence":"additional","affiliation":[{"name":"Department of Microbiology Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Microbiology Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Ehime University Cell\u2010Free Science and Technology Research Center Division of Proteomedical Sciences; Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Ehime University Cell\u2010Free Science and Technology Research Center Division of Proteomedical Sciences; Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Sawasaki","sequence":"additional","affiliation":[{"name":"Ehime University Cell\u2010Free Science and Technology Research Center Division of Proteomedical Sciences; Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaeta","family":"Endo","sequence":"additional","affiliation":[{"name":"Ehime University Cell\u2010Free Science and Technology Research Center Division of Proteomedical Sciences; Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070829"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000140721.27004.4B"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808431"},{"key":"e_1_2_7_5_1","first-page":"581","article-title":"The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta\u2010analysis of individual data from 27 randomised trials","volume":"380","author":"Mihaylova B.","journal-title":"Lancet"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60104-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60697-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1001\/jama.2010.1322","article-title":"Comparative determinants of 4\u2010year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis","volume":"304","author":"Bhatt D. 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