Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels
Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels
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DOI：
10.1096/fj.12-222653
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发表时间：
2013-09-01
期刊：
影响因子：
4.8
通讯作者：
Endo, Yaeta
中科院分区：
文献类型：
--
作者：
Ishigami, Tomoaki;Abe, Kaito;Endo, Yaeta
动脉粥样硬化疾病，如冠状动脉疾病和外周动脉疾病，是全身性疾病，是全世界死亡率和发病率的主要原因之一。然而，动脉粥样硬化发展的确切病理生理机制仍不清楚;目前，动脉粥样硬化被认为涉及炎症过程。全身性炎症反应和免疫细胞在动脉粥样硬化病变原位的积累被认为是必不可少的。我们已经全面分析了动脉粥样硬化患者的自身抗体，通过一个新开发的高通量自身抗体分析系统。动脉粥样硬化患者血清中存在多种自身抗体。在我们用常规技术对每种自身抗体的滴度进行统计分析后，对结果进行了基于自然语言处理的文本挖掘分析。联合分析显示抗白细胞介素（IL）-5抗体与动脉粥样硬化密切相关。抗IL-5抗体滴度和血清IL-5浓度也与其他危险因素密切相关，如低密度脂蛋白胆固醇、血清肌酐、空腹血糖、性别和年龄，表明动脉粥样硬化患者中自身抗体介导的IL-5功能抑制在疾病过程中起重要作用。为了验证这些发现的临床意义，我们计算了抗IL-5自身抗体滴度对人类动脉粥样硬化的特异性和敏感性。当假定抗体滴度为1.49时预测动脉粥样硬化的存在时，灵敏度为95.0%，特异性为91.0%，曲线下面积为0.940。我们的研究结果为理解自身抗体介导的免疫反应在人类动脉粥样硬化中的作用提供了重要线索，并为该疾病的管理提供了新的治疗机会。Abe，K.，青木岛Minegishi，S.，Ryo，A.，Matsunaga，S.，Matsuoka，K.，Takeda，H.，Sawasaki，T.，Umemura，S.，和Endo，Y.抗白细胞介素-5和多种自身抗体与人类动脉粥样硬化疾病和血清白细胞介素-5水平相关。
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.Ishigami, T., Abe, K., Aoki, I., Minegishi, S., Ryo, A., Matsunaga, S., Matsuoka, K., Takeda, H., Sawasaki, T., Umemura, S., and Endo, Y. Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.