Yoshida Yoichi, Wang Hao, Hiwasa Takaki, Machida Toshio, Kobayashi Eiichi, Mine Seiichiro, Tomiyoshi Go, Nakamura Rika, Shinmen Natsuko, Kuroda Hideyuki, Takizawa Hirotaka, Kashiwado Koichi, Kamitsukasa Ikuo, Shin Hideo, Wada Takeshi, Aotsuka Akiyo, Nishi Eiichiro, Ohno Mikiko, Takemoto Minoru, Yokote Koutaro, Takahashi Sho, Matsushima Jun, Zhang Xiao-Meng, Takiguchi Masaki, Iwadate Yasuo
Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Oncotarget. 2017 Dec 24;9(10):8836-8848. doi: 10.18632/oncotarget.23653. eCollection 2018 Feb 6.
Disease 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.
To 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 ( = 192 and = 906 in the second screening and validation cohort, respectively).
First screening identified 3 candidate antigens. Of these, programmed cell death 11 (PDCD11) was determined to be associated with stroke ( < 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, = 0.0039] was not inferior to other known risk factors for ischemic stroke, including age (OR: 4.97, 95% CI: 2.67-9.48, < 0.0001); hypertension (OR: 3.21, 95% CI: 1.76-5.86, = 0.0001); and diabetes (OR: 4.31, 95% CI: 1.74-11.2, = 0.0015).
Serum PDCD11-Ab level may serve as a potential biomarker for TIA.
在患有动脉粥样硬化相关疾病（如脑梗死、心血管疾病）的患者血清中已检测到疾病特异性自身抗体。在本研究中，我们旨在鉴定与短暂性脑缺血发作（TIA）相关的新型自身抗体，TIA是脑梗死的前驱病症。
为了鉴定候选抗原，我们使用20例TIA患者的血清筛选了人主动脉内皮细胞cDNA文库。在2个独立的患者/健康供体（HD）队列中（第二次筛选和验证队列中分别为n = 192和n = 906），使用放大发光邻近均相分析-酶联免疫吸附测定（AlphaLISA）测量血清抗体水平。
首次筛选鉴定出3种候选抗原。其中，细胞程序性死亡11（PDCD11）被确定与中风相关（P < 0.0001），这在使用AlphaLISA的第二次筛选中得到证实。验证队列显示，TIA患者中针对PDCD11的抗体水平（PDCD11-Ab水平）显著高于HDs。多变量逻辑回归分析表明，PDCD11-Ab水平对TIA的预测价值[比值比（OR）：2.44，95%置信区间（CI）：1.33 - 4.57，P = 0.0039]不低于缺血性中风的其他已知危险因素，包括年龄（OR：4.97，95%CI：2.67 - 9.48，P < 0.0001）；高血压（OR：3.21，95%CI：1.76 - 5.86，P = 0.0001）；和糖尿病（OR：4.31，95%CI：1.74 - 11.2，P = 0.0015）。
血清PDCD11-Ab水平可能作为TIA的潜在生物标志物。
