Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack

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

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Oncotarget. 2018; 9:8836-8848. https://doi.org/10.18632/oncotarget.23653

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Abstract

Yoichi Yoshida1,2,3, Hao Wang2,4, Takaki Hiwasa2, Toshio Machida5, Eiichi Kobayashi1,3, Seiichiro Mine5,6, Go Tomiyoshi2,7, Rika Nakamura2,7, Natsuko Shinmen2,7, Hideyuki Kuroda7, Hirotaka Takizawa8, Koichi Kashiwado9, Ikuo Kamitsukasa10,11, Hideo Shin12, Takeshi Wada13, Akiyo Aotsuka13, Eiichiro Nishi14, Mikiko Ohno14, Minoru Takemoto15, Koutaro Yokote15, Sho Takahashi16, Jun Matsushima17, Xiao-Meng Zhang2, Masaki Takiguchi2 and Yasuo Iwadate1

1 Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

2 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan

3 Comprehensive Stroke Center, Chiba University Hospital, Chiba, Japan

4 Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, P. R. China

5 Department of Neurosurgery, Chiba Cerebral and Cardiovascular Center, Ichihara, Chiba, Japan

6 Department of Neurosurgery, Sawara Prefectural Hospital, Chiba, Japan

7 Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, Japan

8 Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, Japan

9 Department of Neurology, Kashiwado Hospital, Chiba, Japan

10 Department of Neurology, Chiba Rosai Hospital, Chiba, Japan

11 Department of Neurology, Chibaken Saiseikai Narashino Hospital, Chiba, Japan

12 Department of Neurosurgery, Higashi Funabashi Hospital, Chiba, Japan

13 Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan

14 Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan

15 Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

16 Clinical Research Center, Chiba University Hospital, Chiba, Japan

17 Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan

Correspondence to:

Takaki Hiwasa, email:

Keywords: TIA; PDCD11; cerebral infarction; autoantibody; biomarker; Gerotarget

Received: August 08, 2017 Accepted: November 16, 2017 Published: December 24, 2017

Abstract

Background: 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.

Methods: 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 (n = 192 and n = 906 in the second screening and validation cohort, respectively).

Results: First 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).

Conclusion: Serum PDCD11-Ab level may serve as a potential biomarker for TIA.


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