Stroke Center, the First Affiliated Hospital, Jinan University, NO. 613, West Huangpu Ave., Tianhe Dist., Guangzhou, 510630, China.
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
BMC Neurol. 2021 Jul 9;21(1):274. doi: 10.1186/s12883-021-02301-w.
Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers.
In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined.
The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis.
ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.
缺血性脑卒中，包括短暂性脑缺血发作（TIA）和急性脑梗死（aCI），是老龄化社会的严重健康问题。因此，本研究旨在寻找 TIA 和 aCI 的生物标志物。
通过使用人主动脉内皮细胞 cDNA 文库，筛选 19 例 TIA 患者血清 IgG 自身抗体识别的候选抗原。通过放大发光接近均相测定联免疫吸附法（AlphaLISA），检测健康供者（HD）、TIA 和 aCI 队列（n=285、92 和 529）中候选抗原的血清抗体水平。还检测了日本公共卫生中心前瞻性队列研究（1991-1993 年）中的血浆抗体水平。
候选抗原为醛缩酶 A（ALDOA）和延胡索酸水合酶（FH）。在 AlphaLISA 中，TIA 或 aCI 患者的抗 ALDOA 抗体（ALDOA-Ab）和抗 FH 抗体（FH-Ab）水平高于 HD（P<0.05）。在多变量逻辑回归分析中，ALDOA-Ab（比值比[OR]：2.46，P=0.0050）和 FH-Ab（OR：2.49，P=0.0037）水平是 TIA 的独立预测因子。根据病例对照研究，ALDOA-Ab（OR：2.50，P<0.01）和 FH-Ab（OR：2.60，P<0.01）水平与 aCI 风险相关。在相关性分析中，ALDOA-Abs 和 FH-Abs 均与高血压、冠心病和习惯性吸烟密切相关。这些抗体水平也与最大内中膜厚度（反映动脉粥样硬化狭窄）密切相关。
ALDOA-Abs 和 FH-Abs 可能是预测动脉粥样硬化性 TIA 和 aCI 的新型潜在生物标志物。
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