Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction

Abstract Background: Ischemic stroke, such as transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and aCI are attempted. Methods: Candidate antigens recognized by IgG autoantibodies in the serum of 19 TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and aCI cohorts ( n = 285, 92 and 529). The antibody levels in the sera of the Japan Public Health Center-based Prospective Cohort Study (JPHC) from 1991 to 1993 was also examined. Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that the levels of anti-ALDOA antibodies (ALDOA-Abs) and anti-FH antibodies (FH-Abs) were both higher in patients with TIA or aCI than those in HDs ( P < 0.05). The levels of ALDOA-Abs [odds ratio (OR): 2.46, P = 0.0050] and FH-Abs (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis. The case-control study showed the levels of ALDOA-Abs (OR: 2.50, P < 0.01) and FH-abs (OR: 2.60, P < 0.01) were associated with risk of aCI. Correlation analysis demonstrated that both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease and habitual smoking. These antibody levels were also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. Conclusions: ALDOA-Abs and FH-Abs can serve as novel potential biomarkers for prediction of atherosclerotic TIA and aCI.