Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
Comprehensive Stroke Center, Chiba University Hospital, Chiba, 260-8677, Japan.
Sci Rep. 2021 Jun 29;11(1):13450. doi: 10.1038/s41598-021-92786-9.
Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.
动脉粥样硬化被认为是全世界发病率、死亡率和残疾的主要原因。抗原标志物的首次筛选是通过重组 cDNA 表达克隆的血清学鉴定进行的，该鉴定确定衔接蛋白相关蛋白复合物 3 亚基 delta 1 (AP3D1) 为动脉粥样硬化患者血清 IgG 抗体识别的抗原。使用作为抗原的重组蛋白，通过扩增发光近同相分析联免疫吸附测定法 (AlphaLISA) 检查血清抗体水平。结果表明，与健康供体相比，急性缺血性脑卒中 (AIS)、短暂性脑缺血发作、糖尿病 (DM)、心血管疾病、慢性肾脏病 (CKD)、食管鳞状细胞癌 (ESCC) 和结直肠癌患者的血清 AP3D1 抗体水平更高。使用受试者工作特征曲线分析计算的 DM、CKD 肾硬化型和 ESCC 的曲线下面积值高于其他疾病。相关性分析表明，抗 AP3D1 抗体水平与最大内膜中层厚度高度相关，表明该标志物反映了动脉粥样硬化的发展。日本公共卫生中心前瞻性研究的结果表明，该抗体标志物可作为 AIS 的危险因素。
