Heliyon (Aug 2020)
Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases
- Yoichi Yoshida,
- Xiao-Meng Zhang,
- Hao Wang,
- Toshio Machida,
- Seiichiro Mine,
- Eiichi Kobayashi,
- Akihiko Adachi,
- Tomoo Matsutani,
- Ikuo Kamitsukasa,
- Takeshi Wada,
- Akiyo Aotsuka,
- Katsuro Iwase,
- Go Tomiyoshi,
- Rika Nakamura,
- Natsuko Shinmen,
- Hideyuki Kuroda,
- Hirotaka Takizawa,
- Koichi Kashiwado,
- Hideo Shin,
- Yuichi Akaogi,
- Junichiro Shimada,
- Eiichiro Nishi,
- Mikiko Ohno,
- Minoru Takemoto,
- Koutaro Yokote,
- Kenichiro Kitamura,
- Yasuo Iwadate,
- Takaki Hiwasa
Affiliations
- Yoichi Yoshida
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
- Xiao-Meng Zhang
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Hao Wang
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou 510632, PR China
- Toshio Machida
- Department of Neurosurgery, Chiba Cerebral and Cardiovascular Center, Ichihara, 290-0512, Chiba, Japan; Department of Neurosurgery, Eastern Chiba Medical Center, Chiba 283-8686, Japan
- Seiichiro Mine
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Neurosurgery, Chiba Cerebral and Cardiovascular Center, Ichihara, 290-0512, Chiba, Japan; Department of Neurosurgery, Sawara Prefectural Hospital, Chiba 287-0003, Japan
- Eiichi Kobayashi
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
- Akihiko Adachi
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
- Tomoo Matsutani
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
- Ikuo Kamitsukasa
- Department of Neurology, Chiba Rosai Hospital, Chiba 290-0003, Japan; Department of Neurology, Chibaken Saiseikai Narashino Hospital, Chiba 275-8580, Japan
- Takeshi Wada
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba 260-0852, Japan
- Akiyo Aotsuka
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba 260-0852, Japan
- Katsuro Iwase
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Go Tomiyoshi
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan
- Rika Nakamura
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan
- Natsuko Shinmen
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan
- Hideyuki Kuroda
- Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan
- Hirotaka Takizawa
- Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba 260-0025, Japan
- Koichi Kashiwado
- Department of Neurology, Kashiwado Hospital, Chiba 260-0854, Japan
- Hideo Shin
- Department of Neurosurgery, Higashi Funabashi Hospital, Chiba 274-0065, Japan
- Yuichi Akaogi
- Department of Neurology, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan
- Junichiro Shimada
- Department of Neurology, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan
- Eiichiro Nishi
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Pharmacology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Mikiko Ohno
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Pharmacology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Minoru Takemoto
- Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan
- Koutaro Yokote
- Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Kenichiro Kitamura
- Department of Internal Medicine 3, University of Yamanashi School of Medicine, Yamamashi 409-3898, Japan
- Yasuo Iwadate
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
- Takaki Hiwasa
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan; Corresponding author.
- Journal volume & issue
-
Vol. 6,
no. 8
p. e04661
Abstract
Background: Serum antibody markers have been increasingly identified not only for cancer and autoimmune diseases but also for atherosclerosis-related diseases such as acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD). Biomarkers for transient ischemic attack (TIA) and non-ST segment elevation acute coronary syndrome (NSTEACS) are potentially useful for detection of early phase of atherosclerotic changes against AIS and AMI, respectively. Methods: We utilized serological identification of antigens by recombinant cDNA expression cloning (SEREX) using a human aortic endothelial cell cDNA phage library and sera from patients with TIA or NSTEACS. Serum antibody levels were measured by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using purified recombinant antigens. Results: Screening of sera from patients with TIA identified DnaJ heat shock protein family (Hsp40) member C2 (DNAJC2) as a candidate antigen, which was also isolated by SEREX screening using sera of patients with NSTEACS. The validation cohort revealed significantly higher DNAJC2 antibody (DNAJC2-Ab) levels in the sera of patients with TIA or AIS than those in healthy donors (HDs). Multivariate logistic regression analysis indicated that the predictive odds ratios (OR) of DNAJC2-Ab levels for TIA and AIS were 2.54 (95% confidence interval [CI]: 1.36–4.74, p = 0.0034) and 2.14 (95% CI: 1.39–3.30, p = 0.0005), respectively. Serum DNAJC2-Ab levels were also higher in patients with AMI, DM, and CKD than those in HDs. Conclusion: Serum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI.
