title: Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.
abstract: Atherosclerotic diseases, such as coronary artery disease and peripheral artery disease, are systemic disorders and among the leading causes of mortality and morbidity throughout the world. 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 in situ are considered essential. We have comprehensively analyzed autoantibodies in patients with atherosclerosis by means of a newly developed high-throughput 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-mining analyses based on natural language processing. Combinatory analysis revealed a close association between anti-interleukin (IL)-5 antibody and atherosclerosis. Titers of anti-IL-5 antibodies and serum IL-5 concentrations were also closely associated with other risk factors, such as low-density lipoprotein cholesterol, serum creatinine, fasting plasma glucose, gender, and age, suggesting that suppressed IL-5 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-IL-5 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-mediated immune reactions in human atherosclerosis and suggest novel therapeutic opportunities for management of the disease.
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Medical Science and Cardio-renal Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama-city, Kanagawa-ken, 236-0004, Japan. tommmish@hotmail.com
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishigami
authors.forename: Kaito
authors.initials: K
authors.lastname: Abe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Minegishi
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Yaeta
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000097:blood* / Q000276:immunology*; D008297:Male; D058729:Peripheral Arterial Disease / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; D008078:Cholesterol, LDL; D015848:Interleukin-5
keywords: autoimmune; coronary heart disease; cytokine; peripheral artery disease