抗集落刺激因子2的动脉粥样硬化相关血清抗体在预测急性缺血性卒中发病及结直肠癌预后中的应用

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

作者信息

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

机构信息

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

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

出版信息

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

DOI:10.3389/fcvm.2023.1042272

PMID:36844744

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9954151/

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 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.

摘要

引言

抗炎症细胞因子自身抗体可用于预防动脉粥样硬化。临床前研究认为集落刺激因子2（CSF2）是一种与动脉粥样硬化和癌症存在因果关系的关键细胞因子。我们检测了动脉粥样硬化或实体癌患者血清中的抗CSF2抗体水平。

方法

基于对重组谷胱甘肽S-转移酶融合CSF2蛋白或CSF2衍生肽作为抗原的识别，采用放大发光邻近均相分析联免疫吸附测定法测量血清抗CSF2抗体水平。

结果

与健康供者（HD）相比，急性缺血性卒中（AIS）、急性心肌梗死（AMI）、糖尿病（DM）和慢性肾脏病（CKD）患者的血清抗CSF2抗体（s-CSF2-Ab）水平显著更高。此外，s-CSF2-Ab水平与内膜中层厚度和高血压相关。对来自一项基于日本公共卫生中心的前瞻性研究的样本分析表明，s-CSF2-Ab可作为AIS的危险因素。此外，食管癌、结直肠癌、胃癌和肺癌患者的s-CSF2-Ab水平高于HD，但乳腺癌患者则不然。此外，s-CSF2-Ab水平与结直肠癌（CRC）术后不良预后相关。在CRC中，尽管抗p53抗体（p53-Ab）水平与总生存期缺乏显著相关性，但s-CSF2-Ab水平与p53-Ab阴性CRC患者的不良预后关联更为密切。