Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer

Shu-Yang Li; Yoichi Yoshida; Masaaki Kubota; Bo-Shi Zhang; Tomoo Matsutani; Masaaki Ito; Satoshi Yajima; Kimihiko Yoshida; Seiichiro Mine; Toshio Machida; Aiko Hayashi; Minoru Takemoto; Koutaro Yokote; Mikiko Ohno; Eiichiro Nishi; Kenichiro Kitamura; Ikuo Kamitsukasa; Hirotaka Takizawa; Mizuki Sata; Kazumasa Yamagishi; Hiroyasu Iso; Norie Sawada; Shoichiro Tsugane; Katsuro Iwase; Hideaki Shimada; Yasuo Iwadate; Takaki Hiwasa

doi:10.3389/fcvm.2023.1042272

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer

Front Cardiovasc Med. 2023 Feb 10:10:1042272. doi: 10.3389/fcvm.2023.1042272. eCollection 2023.

Authors

Shu-Yang Li^{1

2}, Yoichi Yoshida^{1

3}, Masaaki Kubota^{1

2}, Bo-Shi Zhang¹, Tomoo Matsutani¹, Masaaki Ito⁴, Satoshi Yajima⁵, Kimihiko Yoshida⁵, Seiichiro Mine^{1

6

7}, Toshio Machida^{1

7

8}, Aiko Hayashi⁹, Minoru Takemoto^{9

10}, Koutaro Yokote⁹, Mikiko Ohno^{11

12}, Eiichiro Nishi^{11

12}, Kenichiro Kitamura¹³, Ikuo Kamitsukasa¹⁴, Hirotaka Takizawa¹⁵, Mizuki Sata^{16

17}, Kazumasa Yamagishi¹⁶, Hiroyasu Iso¹⁸, Norie Sawada¹⁹, Shoichiro Tsugane¹⁹, Katsuro Iwase², Hideaki Shimada^{4

5}, Yasuo Iwadate^{1

3}, Takaki Hiwasa^{1

2

3

4}

Affiliations

¹ Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
² Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
³ Comprehensive Stroke Center, Chiba University Hospital, Chiba, Japan.
⁴ Department of Clinical Oncology, Toho University Graduate School of Medicine, Tokyo, Japan.
⁵ Department of Gastroenterological Surgery, Toho University Graduate School of Medicine, Tokyo, Japan.
⁶ Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba, Japan.
⁷ Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba, Japan.
⁸ Department of Neurosurgery, Eastern Chiba Medical Center, Chiba, Japan.
⁹ Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹⁰ Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba, Japan.
¹¹ Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹² Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
¹³ Kitakurihama Takuchi Clinic, Yokosuka, Kanagawa, Japan.
¹⁴ Department of Neurology, Chiba Rosai Hospital, Chiba, Japan.
¹⁵ Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, Japan.
¹⁶ Department of Public Health Medicine, Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan.
¹⁷ Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
¹⁸ Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁹ Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.

Abstract

Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer.

Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen.

Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival.

Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Keywords: acute ischemic stroke; antibody biomarker; atherosclerosis; colony-stimulating factor 2; colorectal cancer.

Copyright © 2023 Li, Yoshida, Kubota, Zhang, Matsutani, Ito, Yajima, Yoshida, Mine, Machida, Hayashi, Takemoto, Yokote, Ohno, Nishi, Kitamura, Kamitsukasa, Takizawa, Sata, Yamagishi, Iso, Sawada, Tsugane, Iwase, Shimada, Iwadate and Hiwasa.