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

BMC Neurol. 2021 Jul 9;21(1):274. doi: 10.1186/s12883-021-02301-w.


Background: Ischemic 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.

Methods: In 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.

Results: The 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.

Conclusions: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.

Keywords: ALDOA; Antibody biomarker; Cerebral infarction; FH; Transient ischemic attack.

MeSH terms

  • Autoantibodies / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Cerebral Infarction* / blood
  • Cerebral Infarction* / epidemiology
  • Fructose-Bisphosphate Aldolase / immunology
  • Humans
  • Ischemic Attack, Transient* / blood
  • Ischemic Attack, Transient* / epidemiology


  • Autoantibodies
  • Biomarkers
  • ALDOA protein, human
  • Fructose-Bisphosphate Aldolase