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 SugimotoHirotaka Takizawa, Koichi Kashiwado, Hideo Shin, Go Tomiyoshi, Rika Nakamura, Natsuko Shinmen, Hideyuki Kuroda, Anding Xu, Takaki Hiwasa

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number274
JournalBMC Neurology
Volume21
Issue number1
DOIs
Publication statusPublished - 2021 Dec
Externally publishedYes

Keywords

  • ALDOA
  • Antibody biomarker
  • Cerebral infarction
  • FH
  • Transient ischemic attack

ASJC Scopus subject areas

  • Clinical Neurology

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