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

// Hao Wang 1,2 , Xiao-Meng Zhang 1 , Go Tomiyoshi 1,3 , Rika Nakamura 1,3 , Natsuko Shinmen 1,3 , Hideyuki Kuroda 3 , Risa Kimura 1 , Seiichiro Mine 4,5,6 , Ikuo Kamitsukasa 7,8 , Takeshi Wada 9 , Akiyo Aotsuka 9 , Yoichi Yoshida 1,4 , Eiichi Kobayashi 4 , Tomoo Matsutani 4 , Yasuo Iwadate 4 , Kazuo Sugimoto 1,10 , Masahiro Mori 10 , Akiyuki Uzawa 10 , Mayumi Muto 10 , Satoshi Kuwabara 10 , Minoru Takemoto 11 , Kazuki Kobayashi 11 , Harukiyo Kawamura 11 , Ryoichi Ishibashi 11 , Koutaro Yokote 11 , Mikiko Ohno 12,13 , Po-Min Chen 12 , Eiichiro Nishi 12,13 , Koh Ono 12 , Takeshi Kimura 12 , Toshio Machida 6 , Hirotaka Takizawa 14 , Koichi Kashiwado 15 , Hideaki Shimada 16 , Masaaki Ito 16 , Ken-Ichiro Goto 1 , Katsuro Iwase 1 , Hiromi Ashino 1 , Akiko Taira 1 , Emiko Arita 1 , Masaki Takiguchi 1 and Takaki Hiwasa 1 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 Abstract 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.