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

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

doi:10.1038/s41598-021-92786-9

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.

Highlights

The antibody levels in the sera of CKD patients were examined, which were assumed to be closely related to atherosclerosis
No significant difference was found in the positive rates and the area under the curve (AUC) values between AIS and TIA
Correlation analysis was performed using a Spearman application in order to determine the correlation between s-AP3D1-Ab levels and subject parameters, including general information such as age, body height, weight, body mass index (BMI), and the degree of artery stenosis [the maximum intima-media thickness]

Summary

Introduction

The antibody levels in the sera of CKD patients were examined, which were assumed to be closely related to atherosclerosis. The sera of the CKD patients were obtained from the Kumamoto cohort[22,23], including 145 from patients with diabetic kidney disease (type 1 CKD), 32 from patients with nephrosclerosis (type 2 CKD), and 123 from patients with glomerulonephritis (type 3 CKD). The sera of HDs (82 specimens) were obtained from Chiba University, Chiba Prefectural Sawa

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Discussion

Conclusion