TY - JOUR
T1 - The diagnostic performance of a novel ELISA for human CTP (Cochlin-tomoprotein) to detect perilymph leakage
AU - Ikezono, Tetsuo
AU - Matsumura, Tomohiro
AU - Matsuda, Han
AU - Shikaze, Satomi
AU - Saitoh, Shiho
AU - Shindo, Susumu
AU - Hasegawa, Setsuo
AU - Oh, Seung Ha
AU - Hagiwara, Yoshiaki
AU - Ogawa, Yasuo
AU - Ogawa, Hiroshi
AU - Sato, Hiroaki
AU - Tono, Tetsuya
AU - Araki, Ryuichiro
AU - Maeda, Yukihide
AU - Usami, Shin ichi
AU - Kase, Yasuhiro
N1 - Funding Information:
This work was supported by the Ministry of Health and Welfare, Japan (H26-Nanchitou (Nan)-Ippan-032) (http://www.mhlw.go.jp/english/) (T.I.) and a Grant-in-Aid for the Support Project of Strategic Research Center in Private Universities to the Saitama Medical University Research Center for Genomic Medicine from MEXT of Japan (S1311002). (http://www.mext.go.jp/english/)(T.I.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Prof. Yasushi Okazaki, Saitama Medical University Research Center for Genomic Medicine, for his generous support to our project. We thank Mr. Koichi Toyoda, Industry-University Cooperation Advisor at Saitama Medical University for helping us to establish this clinical trial. We are grateful to Ms. Miki Hatakeyama for editing this manuscript.
Publisher Copyright:
© 2018 Ikezono et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/1
Y1 - 2018/1
N2 - Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient’s condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824–0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.
AB - Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient’s condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824–0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.
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U2 - 10.1371/journal.pone.0191498
DO - 10.1371/journal.pone.0191498
M3 - Article
C2 - 29377910
AN - SCOPUS:85041167796
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e0191498
ER -
