Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Dec 24;9(10):8836-8848.
doi: 10.18632/oncotarget.23653. eCollection 2018 Feb 6.

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

Yoichi Yoshida  1   2   3 , Hao Wang  2   4 , Takaki Hiwasa  2 , Toshio Machida  5 , Eiichi Kobayashi  1   3 , Seiichiro Mine  5   6 , Go Tomiyoshi  2   7 , Rika Nakamura  2   7 , Natsuko Shinmen  2   7 , Hideyuki Kuroda  7 , Hirotaka Takizawa  8 , Koichi Kashiwado  9 , Ikuo Kamitsukasa  10   11 , Hideo Shin  12 , Takeshi Wada  13 , Akiyo Aotsuka  13 , Eiichiro Nishi  14 , Mikiko Ohno  14 , Minoru Takemoto  15 , Koutaro Yokote  15 , Sho Takahashi  16 , Jun Matsushima  17 , Xiao-Meng Zhang  2 , Masaki Takiguchi  2 , Yasuo Iwadate  1
Affiliations

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

Yoichi Yoshida et al. Oncotarget. .

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.

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

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST This work was performed in collaboration with Fujikura Kasei Co., Ltd. GT, RN, NS and HK are employees of Fujikura Kasei Co., Ltd.

Figures

Figure 1
Figure 1. First screening by SEREX and Western blot analysis
Recombinant proteins were blotted onto nitrocellulose membranes and reacted with patient serum. Arrows indicate positive phage clones. Positive clones were re-cloned for 2 additional times to obtain monoclonality A. GST protein (lane 1) and affinity-purified GST-tagged PDCD11 (lane 2) were separated on 11% SDS-polyacrylamide gels and stained with Coomassie Blue B., or western blotted using anti-GST antibody C., or the autologous sera of patients with aCI D., TIA E., and HD F. Asterisks indicate partially degraded proteins. Molecular weights are shown in the left.
Figure 2
Figure 2. Serum antibody levels against SEREX antigens examined by AlphaLISA
Antibody levels against 3 antigen candidates, PDCD11 A., CTNNA1 B., and ACTR3B C., were compared between HDs and patients with aCI in second screening cohort. Alpha counts represent relative antibody levels. ***p < 0.0001 and p = 0.2033 were calculated by Mann–Whitney U test. D. The levels of PDCD11-Abs examined by AlphaLISA in the validation cohort. The PDCD11-Ab levels were compared between HDs and patients with TIA, aCI, or cCI. ***p < 0.001 was calculated by Mann–Whitney U test with type I error adjustment using Bonferroni procedure and not significant (n.s.), p = 1 was calculated by Kruskal–Wallis test with type I error adjustment using Bonferroni procedure. HD, healthy donors; P, patients with acute cerebral infarction; TIA, transient ischemic attack; aCI, acute cerebral infarction; cCI, chronic cerebral infarction; Ab, antibody.
Figure 3
Figure 3. Immunohistochemistry
Surgically-resected ischemic brain tissue was stained with hematoxylin only A., and anti-PDCD11 antibody (B., arrows).
See this image and copyright information in PMC

References

    1. Hao Y, Tian S, Sun M, Zhu Y, Nie Z, Yang S. Association between matrix metalloproteinase gene polymorphisms and development of ischemic stroke. Int J Clin Exp Pathol. 2015;8:11647–11652. - PMC - PubMed
    1. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen Nv, Chopp M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106:829–838. - PMC - PubMed
    1. Chen B, Zhang F, Li QY, Gong A, Lan Q. Protective effect of Ad-VEGF-Bone mesenchymal stem cells on cerebral infarction. Turk Neurosurg. 2016;26:8–15. - PubMed
    1. Ross R, Glomset JA. The pathogensis of atherosclerosis. N Engl J Med. 1976;295:369–377. - PubMed
    1. Ross R. Atherosclerosis — an inflamematory disease. N Engl J Med. 1999;340:115–126. - PubMed