Abstract
BackgroundDisease specific autoantibodies have been detected in the sera of patients with atherosclerosis-related diseases, such as cerebral infarction, cardiovascular disease. In the present study, we aimed to identify novel autoantibodies responsible for transient ischemic attack (TIA), a prodromal condition for cerebral infarction.MethodsTo identify candidate antigens, we screened a human aortic endothelial cell cDNA library using sera from 20 patients with TIA. Serum antibody levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 2 independent patient/healthy donor (HD) cohorts (n = 192 and n = 906 in the second screening and validation cohort, respectively).ResultsFirst screening identified 3 candidate antigens. Of these, programmed cell death 11 (PDCD11) was determined to be associated with stroke (p < 0.0001), as evidenced from the second screening using AlphaLISA. The validation cohort revealed significantly higher antibody levels against PDCD11 (PDCD11-Ab levels) in patients with TIA than in HDs. Multivariate logistic regression analysis indicated that the predictive value of PDCD11-Ab levels for TIA [Odds ratio (OR): 2.44, 95% confidence interval (CI): 1.33-4.57, p = 0.0039] was not inferior to other known risk factors for ischemic stroke, including age (OR: 4.97, 95% CI: 2.67–9.48, p < 0.0001); hypertension (OR: 3.21, 95% CI: 1.76–5.86, p = 0.0001); and diabetes (OR: 4.31, 95% CI: 1.74–11.2, p = 0.0015).ConclusionSerum PDCD11-Ab level may serve as a potential biomarker for TIA.
Highlights
Ischemic stroke is one of the major causes of mortality and morbidity worldwide, and one of the primary pathological processes responsible for stroke is atherosclerosis [1,2,3]
Serum programmed cell death 11 (PDCD11)-Ab level may serve as a potential biomarker for transient ischemic attack (TIA)
Proposed antigenic proteins related to atherogenesis that may be recognized by the immune system are oxidized low density lipoprotein, phosphorylcholine, heat shock proteins (Hsps), apolipoprotein A-1, and phospholipids [9]
Summary
Ischemic stroke is one of the major causes of mortality and morbidity worldwide, and one of the primary pathological processes responsible for stroke is atherosclerosis [1,2,3]. SEREX has been used to identify more than 1000 novel cancer antigens and is considered one of the most effective methods for identifying antigenic targets on a genomic scale [12,13,14]. This method was originally developed to screen cancer-associated antigens, it has been applied for vascular disorders such as transplant-associated coronary disease [15], Kawasaki disease [16], and moyamoya disease [17]. We aimed to identify novel autoantibodies responsible for transient ischemic attack (TIA), a prodromal condition for cerebral infarction
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