The diagnostic performance of a novel ELISA for human CTP (Cochlin-tomoprotein) to detect perilymph leakage.

Tetsuo Ikezono,Seung Ha Oh,Ryuichiro Araki,Yasuhiro Kase,Tetsuya Tono,Shiho Saitoh,Yoshiaki Hagiwara,Han Matsuda,Yukihide Maeda,Susumu Shindo,Satomi Shikaze,Hiroshi Ogawa,Hiroaki Sato,Tomohiro Matsumura,Shin-Ichi Usami,Setsuo Hasegawa,Yasuo Ogawa

doi:10.1371/journal.pone.0191498

Abstract

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.

Highlights

Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces
PLF is surgically correctable by sealing the fistula, and appropriate recognition and treatment of PLF can improve these symptoms, and in turn, improve the quality of life of afflicted patients
The clinical entity of PLF was initially proposed more than a century ago, yet it has remained a topic of controversy for more than 50 years [5]

Summary

Introduction

Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid (perilymph)-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces. If there is a leakage of perilymph from fistulization, the symptoms may fluctuate and worsen. These potential pathways exist between the perilymphatic space and the middle ear, the actual leaking of fluid can be difficult or impossible to prove. The difficulty of making a definitive diagnosis of PLF due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its prevalence, natural history, management, and even its very existence [5], [6], [7], [8], [9]. PLF is an especially important and treatable disease for otologists

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