Reliability of Serological Prestin Levels in Humans and its Relation to Otoacoustic Emissions, a Functional Measure of Outer Hair Cells

Abstract

Objectives: Serological biomarkers, common to many areas of medicine, have the potential to inform on the health of the human body and to give early warning of risk of compromised function or illness before symptoms are experienced. Serological measurement of prestin, a motor protein uniquely produced and expressed in outer hair cells, has recently been identified as a potential biomarker to inform on the health of the cochlea. Before any test can be introduced into the clinical toolkit, the reproducibility of the measurement when repeated in the same subject must be considered. The primary objective of this study is to outline the test-retest reliability estimates and normative ranges for serological prestin in healthy young adults with normal hearing. In addition, we examine the relation between serum prestin levels and otoacoustic emissions (OAEs) to compare this OHC-specific protein to the most common measure of OHC function currently used in hearing assessments. Design: We measured prestin levels serologically from circulating blood in 34 young adults (18 to 24 years old) with clinically normal pure-tone audiometric averages at five different timepoints up to six months apart (average intervals between measurements ranged from <1 week to 7 weeks apart). To guide future studies of clinical populations, we present the standard error of the measurement, reference normative values, and multiple measures of reliability. Additionally, we measured transient evoked OAEs at the same five timepoints and used correlation coefficients to examine the relation between OAEs and prestin levels (pg/mL). Results: Serum prestin levels demonstrated good to excellent reliability between and across the five different time points, with correlation coefficients and intraclass correlations >0.8. Across sessions, the average serum prestin level was 250.20 pg/mL, with a standard error of measurement of 7.28 pg/mL. Moreover, positive correlations (generally weak to moderate) were found between prestin levels and OAE magnitudes and signal-to-noise ratios. Conclusions: Findings characterize serum prestin in healthy young adults with normal hearing and provide initial normative data that may be critical to interpreting results from individuals with sensorineural hearing loss. Our results demonstrate reliability of serum prestin levels in a sample of normal-hearing young adults across five test sessions up to 6 months apart, paving the way for testing larger samples to more accurately estimate test-retest standards for clinical protocols, including those involving serial monitoring. The positive correlations between serum prestin and OAE levels, although weak to moderate, reinforce that the source of serum prestin is likely the outer hair cells in the inner ear, but also that serum prestin and OAEs each may also index aspects of biologic function not common to the other.

Noise exposure levels predict blood levels of the inner ear protein prestin

“…Previous reports suggested that EHF audiometry is generally better than standard audiometry and OAEs at detecting the early stages, i.e., small levels, of OHC loss 31 , 36 . Moreover, although we previously found a weak correlation between serum prestin levels and TEOAEs 15 , unlike serum prestin, TEOAEs did not correlate with noise exposure levels in the current study. Thus, either noise-related OHC damage is too small to be detected by audiometry and TEOAEs but can be detected by serum prestin levels, or low serum prestin levels in the At-Risk group is being driven by a factor other than OHC loss, as we consider next.…”

“…That is, prestin may be removed from the inner ear as part of the normal proteomic recycling (turnover) processes that maintain cellular homeostasis. Consistent with this proposed homeostatic mechanism, we have previously shown that the healthy ear has stable levels of prestin molecules in circulation 15 . Possible mechanisms for uptake, recycling, and sorting of plasma-membrane proteins, such as prestin in the OHCs.…”

“…The results of our previous studies led us to hypothesize that lower levels of serum prestin could follow cochlear injury and be the result of fewer in-tact OHCs undergoing normal prestin production and turnover 15 , 17 , 18 . In our animal model studies, significant noise-induced loss of OHCs was confirmed histologically and manifested as noise induced changes in distortion product OAE levels and auditory brainstem response thresholds 17 , 18 .…”

“…We have previously used animal models to demonstrate changes to serum prestin after a traumatic noise event that resulted in hearing loss from OHC death 17 , 18 . A parallel literature is also emerging in humans 15 , 19 , 20 . For example, in our recent work in young adults with clinically normal audiograms (the current clinical gold standard for diagnosing sensorineural hearing loss from noise or other sources), we demonstrated that serum prestin levels have high test–retest reliability, using an experimental approach where serum was obtained at five time points over the span of multiple months 15 .…”

“…A parallel literature is also emerging in humans 15 , 19 , 20 . For example, in our recent work in young adults with clinically normal audiograms (the current clinical gold standard for diagnosing sensorineural hearing loss from noise or other sources), we demonstrated that serum prestin levels have high test–retest reliability, using an experimental approach where serum was obtained at five time points over the span of multiple months 15 . We found that while serum prestin levels were stable over this time window on the individual level, there was considerable between-subject variation, despite all participants having clinically normal audiometric function.…”