BMC Neurology (Jul 2021)

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

  • Hao Wang,
  • Hao Lu,
  • Xiao-Meng Zhang,
  • Ken-ichiro Goto,
  • Eiichi Kobayashi,
  • Yoichi Yoshida,
  • Akihiko Adachi,
  • Tomoo Matsutani,
  • Yasuo Iwadate,
  • Seiichiro Mine,
  • Toshio Machida,
  • Mizuki Sata,
  • Kazumasa Yamagishi,
  • Hiroyasu Iso,
  • Norie Sawada,
  • Shoichiro Tsugane,
  • Ikuo Kamitsukasa,
  • Takeshi Wada,
  • Akiyo Aotsuka,
  • Kazuo Sugimoto,
  • Hirotaka Takizawa,
  • Koichi Kashiwado,
  • Hideo Shin,
  • Go Tomiyoshi,
  • Rika Nakamura,
  • Natsuko Shinmen,
  • Hideyuki Kuroda,
  • Anding Xu,
  • Takaki Hiwasa

DOI
https://doi.org/10.1186/s12883-021-02301-w
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 13

Abstract

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Abstract 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.

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