Author:
Namiki Toshiki,Takemoto Minoru,Hayashi Aiko,Yamagata Hiroki,Ishikawa Takahiro,Yokote Koutaro,Li Shu-Yang,Kubota Masaaki,Zhang Bo-Shi,Yoshida Yoichi,Matsutani Tomoo,Mine Seiichiro,Machida Toshio,Kobayashi Yoshio,Terada Jiro,Naito Akira,Tatsumi Koichiro,Takizawa Hirotaka,Nakamura Rika,Kuroda Hideyuki,Iwadate Yasuo,Hiwasa Takaki
Abstract
Abstract
Background
Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy.
Methods
Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples.
Results
Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients.
Conclusions
Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.
Funder
This work was supported, in part, by research grants from the Japan Science and Technology Agency (JST) and JSPS KAKENHI
Publisher
Springer Science and Business Media LLC
Subject
General Medicine,Endocrinology, Diabetes and Metabolism
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