Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
Sci Rep. 2021 Nov 5;11(1):21772. doi: 10.1038/s41598-021-01176-8.
The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.
动脉粥样硬化相关疾病患者的血清中存在疾病特异性抗原和自身抗体已被广泛报道,被认为是动脉壁炎症和免疫因素参与的结果。本研究旨在通过对短暂性脑缺血发作(TIA)患者进行重组 cDNA 表达克隆的血清学鉴定,从患者中鉴定出缺血性脑卒中的新型抗体。我们鉴定出丝氨酸蛋白酶抑制剂,E 族成员 1(SERPINE1)作为候选抗原。使用放大发光近同相分析联免疫吸附试验定量的血清抗 SERPINE1 抗体水平在缺血性脑卒中患者中,包括急性脑梗死(ACI)、TIA 和慢性脑梗死患者中明显高于健康供体。抗体水平与年龄较大、女性以及存在高血压、糖尿病和心血管疾病密切相关。年龄和颈动脉内膜中层厚度与抗体水平呈正相关,这表明 SERPINE1 可能反映了动脉粥样硬化的进展。在多变量分析中,SERPINE1 抗体水平是 ACI 的独立预测因子。因此,抗 SERPINE1 抗体的血清水平可能可作为动脉粥样血栓性梗死的生物标志物。