Scientific Reports (Jun 2021)

Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis

  • Shu-Yang Li,
  • Yoichi Yoshida,
  • Eiichi Kobayashi,
  • Masaaki Kubota,
  • Tomoo Matsutani,
  • Seiichiro Mine,
  • Toshio Machida,
  • Yoshiro Maezawa,
  • Minoru Takemoto,
  • Koutaro Yokote,
  • Yoshio Kobayashi,
  • Hirotaka Takizawa,
  • Mizuki Sata,
  • Kazumasa Yamagishi,
  • Hiroyasu Iso,
  • Norie Sawada,
  • Shoichiro Tsugane,
  • Sohei Kobayashi,
  • Kazuyuki Matsushita,
  • Fumio Nomura,
  • Hisahiro Matsubara,
  • Makoto Sumazaki,
  • Masaaki Ito,
  • Satoshi Yajima,
  • Hideaki Shimada,
  • Katsuro Iwase,
  • Hiromi Ashino,
  • Hao Wang,
  • Kenichiro Goto,
  • Go Tomiyoshi,
  • Natsuko Shinmen,
  • Rika Nakamura,
  • Hideyuki Kuroda,
  • Yasuo Iwadate,
  • Takaki Hiwasa

DOI
https://doi.org/10.1038/s41598-021-92786-9
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 15

Abstract

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Abstract 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.