• Yoichi Yoshida, Hao Wang, Takaki Hiwasa, Toshio Machida, Eiichi Kobayashi, Seiichiro Mine, Go Tomiyoshi, Rika Nakamura, Natsuko Shinmen, Hideyuki Kuroda, Hirotaka Takizawa, Koichi Kashiwado, Ikuo Kamitsukasa, Hideo Shin, Takeshi Wada, Akiyo Aotsuka, Eiichiro Nishi, Mikiko Ohno, Minoru Takemoto, Koutaro Yokote, Sho Takahashi, Jun Matsushima, Xiao-Meng Zhang, Masaki Takiguchi, and Yasuo Iwadate.
• Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
• Oncotarget. 2018 Feb 6; 9 (10): 8836-8848.

BackgroundDisease specific autoantibodies have been detected in the sera of patients with atherosclerosis-related diseases, such as cerebral infarction, cardiovascular disease. In the present study, we aimed to identify novel autoantibodies responsible for transient ischemic attack (TIA), a prodromal condition for cerebral infarction.MethodsTo identify candidate antigens, we screened a human aortic endothelial cell cDNA library using sera from 20 patients with TIA. Serum antibody levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 2 independent patient/healthy donor (HD) cohorts (n = 192 and n = 906 in the second screening and validation cohort, respectively).ResultsFirst screening identified 3 candidate antigens. Of these, programmed cell death 11 (PDCD11) was determined to be associated with stroke (p < 0.0001), as evidenced from the second screening using AlphaLISA. The validation cohort revealed significantly higher antibody levels against PDCD11 (PDCD11-Ab levels) in patients with TIA than in HDs. Multivariate logistic regression analysis indicated that the predictive value of PDCD11-Ab levels for TIA [Odds ratio (OR): 2.44, 95% confidence interval (CI): 1.33-4.57, p = 0.0039] was not inferior to other known risk factors for ischemic stroke, including age (OR: 4.97, 95% CI: 2.67-9.48, p < 0.0001); hypertension (OR: 3.21, 95% CI: 1.76-5.86, p = 0.0001); and diabetes (OR: 4.31, 95% CI: 1.74-11.2, p = 0.0015).ConclusionSerum PDCD11-Ab level may serve as a potential biomarker for TIA.

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