Research Papers: Gerotarget (Focus on Aging):

Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction

Hao Wang, Xiao-Meng Zhang, Go Tomiyoshi, Rika Nakamura, Natsuko Shinmen, Hideyuki Kuroda, Risa Kimura, Seiichiro Mine, Ikuo Kamitsukasa, Takeshi Wada, Akiyo Aotsuka, Yoichi Yoshida, Eiichi Kobayashi, Tomoo Matsutani, Yasuo Iwadate, Kazuo Sugimoto, Masahiro Mori, Akiyuki Uzawa, Mayumi Muto, Satoshi Kuwabara, Minoru Takemoto, Kazuki Kobayashi, Harukiyo Kawamura, Ryoichi Ishibashi, Koutaro Yokote, Mikiko Ohno, Po-Min Chen, Eiichiro Nishi, Koh Ono, Takeshi Kimura, Toshio Machida, Hirotaka Takizawa, Koichi Kashiwado, Hideaki Shimada, Masaaki Ito, Ken-Ichiro Goto, Katsuro Iwase, Hiromi Ashino, Akiko Taira, Emiko Arita, Masaki Takiguchi and Takaki Hiwasa _

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Oncotarget. 2018; 9:5600-5613. https://doi.org/10.18632/oncotarget.23789

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Hao Wang1,2, Xiao-Meng Zhang1, Go Tomiyoshi1,3, Rika Nakamura1,3, Natsuko Shinmen1,3, Hideyuki Kuroda3, Risa Kimura1, Seiichiro Mine4,5,6, Ikuo Kamitsukasa7,8, Takeshi Wada9, Akiyo Aotsuka9, Yoichi Yoshida1,4, Eiichi Kobayashi4, Tomoo Matsutani4, Yasuo Iwadate4, Kazuo Sugimoto1,10, Masahiro Mori10, Akiyuki Uzawa10, Mayumi Muto10, Satoshi Kuwabara10, Minoru Takemoto11, Kazuki Kobayashi11, Harukiyo Kawamura11, Ryoichi Ishibashi11, Koutaro Yokote11, Mikiko Ohno12,13, Po-Min Chen12, Eiichiro Nishi12,13, Koh Ono12, Takeshi Kimura12, Toshio Machida6, Hirotaka Takizawa14, Koichi Kashiwado15, Hideaki Shimada16, Masaaki Ito16, Ken-Ichiro Goto1, Katsuro Iwase1, Hiromi Ashino1, Akiko Taira1, Emiko Arita1, Masaki Takiguchi1 and Takaki Hiwasa1

1 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan

2 Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, P. R. China

3 Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, Japan

4 Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

5 Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba, Japan

6 Department of Neurosurgery, Chiba Cerebral and Cardiovascular Center, Chiba, Japan

7 Department of Neurology, Chiba Rosai Hospital, Chiba, Japan

8 Department of Neurology, Chibaken Saiseikai Narashino Hospital, Chiba, Japan

9 Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan

10 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan

11 Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

12 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

13 Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan

14 Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, Japan

15 Department of Neurology, Kashiwado Hospital, Chiba, Japan

16 Department of Surgery, School of Medicine, Toho University, Tokyo, Japan

Correspondence to:

Takaki Hiwasa, email:

Keywords: TIA; cerebral infarction; SEREX; antibody biomarker; atherosclerosis; Gerotarget

Received: August 12, 2017 Accepted: November 16, 2017 Published: December 31, 2017


Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (P < 0.01). Spearman’s correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI.

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