TY - JOUR
T1 - Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction
AU - Wang, Hao
AU - Lu, Hao
AU - Zhang, Xiao Meng
AU - Goto, Ken ichiro
AU - Kobayashi, Eiichi
AU - Yoshida, Yoichi
AU - Adachi, Akihiko
AU - Matsutani, Tomoo
AU - Iwadate, Yasuo
AU - Mine, Seiichiro
AU - Machida, Toshio
AU - Sata, Mizuki
AU - Yamagishi, Kazumasa
AU - Iso, Hiroyasu
AU - Sawada, Norie
AU - Tsugane, Shoichiro
AU - Kamitsukasa, Ikuo
AU - Wada, Takeshi
AU - Aotsuka, Akiyo
AU - Sugimoto, Kazuo
AU - Takizawa, Hirotaka
AU - Kashiwado, Koichi
AU - Shin, Hideo
AU - Tomiyoshi, Go
AU - Nakamura, Rika
AU - Shinmen, Natsuko
AU - Kuroda, Hideyuki
AU - Xu, Anding
AU - Hiwasa, Takaki
N1 - Funding Information:
The design of this study was supported in part by a research grant from the Japan Agency for Medical Research and Development (AMED) of Japan (Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus). Sample collection, preparation, analysis, and interpretation of data were supported by JSPS KAKENHI (Grant Number: 20K17953, 19K09451, 17K19810, and 17K16626). International collaborative research was supported by Natural Science Foundation of Guangdong Province, China (Grant NO: 2018A0303131003), Science and Technology Program of Guangzhou, China (Grant NO: 201707010449), and Toka-Donghua Educational and Cultural Exchange Foundation, and Setsuro Fujii Memorial of Medical Sciences and The Osaka Foundation for Promotion of Fundamental Medical Research. JPHC Study was supported by National Cancer Center Research and Development Fund (since 2011) and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010).
Funding Information:
The authors would like to thank Prof. Masaki Takiguchi (Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University) for valuable discussion and suggestion.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - ALDOA
KW - Antibody biomarker
KW - Cerebral infarction
KW - FH
KW - Transient ischemic attack
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U2 - 10.1186/s12883-021-02301-w
DO - 10.1186/s12883-021-02301-w
M3 - Article
C2 - 34243715
AN - SCOPUS:85109700335
SN - 1471-2377
VL - 21
JO - BMC Neurology
JF - BMC Neurology
IS - 1
M1 - 274
ER -
