Abstract
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.
Highlights
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
We identified SERPINE1 antibodies in the sera of patients who had a transient ischemic attack (TIA) and investigated whether the SERPINE1 antibody could serve as a novel biomarker of ischemic stroke such as acute cerebral infarction, chronic cerebral infarction, and TIA
Western blotting was performed to demonstrate the presence of anti-SERPINE1 antibody in the serum samples from healthy donors (HDs) (#7021) and patients in the acute cerebral infarction (aCI) (#7074) and TIA groups (#7096)
Summary
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. Vascular endothelial cells are affected by risk factors, and atheroma is formed from various immune cells and chronic inflammation, resulting in the progression of atherosclerosis[2] Antigenic proteins such as oxidized low-density lipoprotein, phosphorylcholine, heat shock proteins, apolipoprotein A1, and phospholipids are involved in this immune response, and the levels of autoantibodies against these proteins are elevated in the sera of patients with atherosclerosis-related diseases such as cerebral infarction, coronary artery disease, and chronic kidney d isease[3,4,5]. We identified SERPINE1 antibodies in the sera of patients who had a transient ischemic attack (TIA) and investigated whether the SERPINE1 antibody could serve as a novel biomarker of ischemic stroke such as acute cerebral infarction (aCI), chronic cerebral infarction (cCI), and TIA
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