Elevation of Autoantibody in Patients with Ischemic Stroke

Abstract

Recent clinical research has revealed a significant correlation between atherosclerosis, one of the primary etiologies of ischemic stroke, and the immune system. Assuming that "disease-specific autoantibodies are produced in the sera of patients with ischemic stroke," we investigated multiple arteriosclerosis-related antibodies using the serological identification of antigens by recombinant cDNA expression cloning (SEREX), an established method for identifying antigenic proteins. We either screened a human aortic endothelial cell cDNA library or conducted protein array screening using the sera from patients with ischemic stroke, such as carotid artery stenosis or transient ischemic attack (TIA). Next, we measured serum antibody levels using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in patient/healthy donor (HD) cohorts and identified several antigens, the antibody levels of which were significantly higher in patients with ischemic stroke than in HDs. This review introduced the method of identifying antigens by the SEREX and protein microarray and summarized antigenic proteins. In particular, it focused on anti-replication protein A2 antibody and anti-programmed cell death 11 antibody, which are significantly related to atherosclerotic plaque and ischemic brain tissue, respectively, and proposed the mechanism of elevated autoantibody levels against them. Furthermore, this review suggests a possibility of clinical application as an atherosclerotic disease diagnostic marker for TIA or cerebral infarction.

Keywords: TIA; atherosclerosis; autoantibody; biomarker; cerebral infarction.

Fig. 1.

Immunohistochemistry. Surgically excised carotid plaque (A–D) was stained with hematoxylin only (A), anti-SMC; which identified vascular smooth muscle cells (B), anti-CD68; which identified macrophages (C, arrow), or anti-RPA2 antibody (D, arrow). Surgically resected ischemic brain tissue (E and F) was stained with hematoxylin only (E) and anti-PDCD11 antibody (F, arrow). Photos reprinted with the permission of BioMed Central journals (A–D) and Oncotarget (E and F).

Fig. 2.

The correlation between autoantibody levels and other atherosclerotic diseases, including AMI and DM. The levels of bRPA2-Ab (A) were examined by AlphaLISA. The mean age ± SDs of HDs and patients with AMI or DM were 58.29 ± 5.63, 58.28 ± 8.5, and 58.37 ± 9.11 years, respectively. ***P < 0.001 was calculated by the Mann–Whitney U-test with type I error adjustment using the Bonferroni procedure. bRPA2-Ab, antibody against peptide antigen of RPA2-132; AMI, acute myocardial infarction; DM, diabetes mellitus; HD, healthy donors.