Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases.

Sep 14, 2020

Contributor: 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

Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases.

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.
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.
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, = 0.0034) and 2.14 (95% CI: 1.39-3.30, = 0.0005), respectively. Serum DNAJC2-Ab levels were also higher in patients with AMI, DM, and CKD than those in HDs.
Serum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI.

© 2020 The Author(s).

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About The Expert

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.

References

PubMed