Abstract
BackgroundIschemic 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.MethodsIn 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.ResultsThe 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.ConclusionsALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.
Highlights
Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction, is a serious health problem in the aging society
The region between amino acids 70 and 469 of aldolase A (ALDOA) and that between amino acids 1 and 185 of fumarate hydratase (FH) were obtained as pBluescript II clones; both were recombined into pGEX-4 T-2 vectors individually
Presence of serum antibodies confirmed by western blotting We aimed at confirming the presence of ALDOA-Abs and FH antibody (FH-Ab) in the serum of patients with TIA or cerebral infarction (CI) through western blotting
Summary
Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. This study aimed to identify TIA and aCI biomarkers. Ischemic stroke, including transient ischemic attack (TIA) and cerebral infarction (CI), is the most globally known cerebrovascular disorder. TIA is a temporary episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [1]. CI is an episode of neurological dysfunction caused by focal brain infarction, often. Patients with TIA are at a high risk of CI. The prevalence of prior TIA in patients with CI was 15–30%. Early TIA diagnosis and CI onset prediction are the key steps to reduce ischemic stroke occurrence [5]
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