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

Serological biomarkers of inner ear proteins are a promising new approach for studying human hearing. Here, we focus on the serological measurement of prestin, a protein integral to a human's highly sensitive hearing, expressed in cochlear outer hair cells (OHCs). Building from recent nonhuman studies that associated noise-induced OHC trauma with reduced serum prestin levels, and studies suggesting subclinical hearing damage in humans regularly engaging in noisy activities, we investigated the relation between serum prestin levels and environmental noise levels in young adults with normal clinical audiograms. We measured prestin protein levels from circulating blood and collected noise level data multiple times over the course of the experiment using body-worn sound recorders. Results indicate that serum prestin levels have a negative relation with noise exposure: individuals with higher routine noise exposure levels tended to have lower prestin levels. Moreover, when grouping participants based on their risk for a clinically-significant noise-induced hearing loss, we found that prestin levels differed significantly between groups, even though behavioral hearing thresholds were similar. We discuss possible interpretations for our findings including whether lower serum levels may reflect subclinical levels of OHC damage, or possibly an adaptive, protective mechanism in which prestin expression is downregulated in response to loud environments.

Screening of 23 candidate genes by next-generation sequencing of patients with permanent congenital hypothyroidism: novel variants in TG, TSHR, DUOX2, FOXE1, and SLC26A7.

PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.

Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead.

BACKGROUND: Some studies in animal models and humans suggest that exposure to lead is associated with hearing loss. Lead can reach the inner ear through the blood circulation; evidence suggests that lead could accumulate in the inner ear, causing inner ear damage. AIM: To evaluate prestin and otolin-1 protein levels and their relationship with an increased hearing threshold in participants exposed to lead. METHODS: We conducted a cross-sectional study with 315 participants from Tlaxcala, Mexico. Blood lead levels (BPb) were evaluated by graphite furnace atomic absorption spectrometry. Serum prestin and otolin-1 were quantified using ELISA. Auditory function at frequencies of 0.125 to 8 kHz was evaluated in a soundproof chamber. RESULTS: Participants were classified according to BPb: group I (<10 µg/dL) had a median BPb of 6 µg/dL and prestin levels of 11.06 ng/mL. While participants in group II (≥10 µg/dL) had a median of BPb 20.7 µg/dL (p < 0.05) and prestin levels of 0.15 ng/mL (p < 0.001). Participants in both groups showed a normal hearing. Otolin-1 levels were higher for participants with normal hearing and lower for participants with hearing loss in both groups, p > 0.05. Multiple linear regression models predict an average decrease of 0.17 to 0.26 ng/mL in prestin levels per decibel increase for the frequencies evaluated. CONCLUSIONS: Participants with high BPb showed an increase in hearing threshold, and prestin levels decreased proportionally to the hearing threshold increase. This is the first study to evaluate prestin as a potential biomarker for hearing damage, evaluated by audiometry, in participants with lead exposure.

Re-visiting autoimmunity to sodium-iodide symporter and pendrin in thyroid disease.

OBJECTIVE: Iodide transport across thyrocytes constitutes a critical step for thyroid hormone biosynthesis, mediated mainly by the basolateral sodium-iodide-symporter (NIS (SLC5A5)) and the apical anion exchanger pendrin (PDS (SLC26A4)). Both transmembrane proteins have been described as autoantigens in thyroid disease, yet the reports on autoantibody (aAb) prevalence and diagnostic usefulness are conflicting. Reasons for the inconclusive findings may be small study groups and principle differences in the technologies used. DESIGN: We decided to re-evaluate this important issue by establishing novel non-radioactive tests using full-length antigens and comparable protocols, and analyzing a large cohort of thyroid patients (n = 323) and control samples (n = 400). METHODS: NIS and PDS were recombinantly expressed as fusion protein with firefly luciferase (Luc). Stably transfected HEK293 cells were used as reproducible source of the autoantigens. RESULTS: Recombinant NIS-Luc showed iodide transport activity, indicating successful expression and correct processing. Commercial antibodies yielded dose-dependent responses in the newly established assays. Reproducibility of assay signals from patient sera was verified with respect to linearity, stability and absence of matrix effects. Prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs 5.0%). NIS-aAb were more prevalent in patients than controls (7.7% vs 1.8%), especially in Graves' Disease (12.3%). Neither NIS-aAb nor PDS-aAb concentrations were related to TPO-aAb or TSH-receptor-aAb concentrations, or to serum zinc or selenium status. CONCLUSIONS: Our data highlight a potential relevance of autoimmunity against NIS for thyroid disease, whereas an assessment of PDS-aAb in thyroid patients seems not to be of diagnostic value (yet).

A Preliminary Report on the Investigation of Prestin as a Biomarker for Idiopathic Sudden Sensorineural Hearing Loss.

To date, no specific biomarkers for idiopathic sudden sensorineural hearing loss (ISSHL) have been used. The aim of this study is to investigate whether prestin, the motor protein of cochlear outer hair cells, could be used as a biomarker candidate for the diagnosis and prognosis judgement of ISSHL. Blood samples of 14 ISSHL patients and 28 control patients without history of hearing loss were collected. Plasma prestin concentration was measured using Human Prestin (SLC26A5) ELISA Kit. The results showed that prestin was detectable in the plasma of all patients and the concentration of prestin was significantly higher in ISSHL patients with about half being above the average range of control patients. Moreover, in treatment responsive group, 6 of 10 patients had decreased prestin levels after treatment compared to those of before treatment, while the prestin levels of all the 4 patients in treatment unresponsive group increased in varying degrees. Our promising preliminary results suggest that prestin has the potential to serve as a biomarker to assist diagnosis and judge response to pharmacological treatments.

Noise-induced trauma produces a temporal pattern of change in blood levels of the outer hair cell biomarker prestin.

Biomarkers in easy-to-access body fluid compartments, such as blood, are commonly used to assess health of various organ systems in clinical medicine. At present, no such biomarkers are available to inform on the health of the inner ear. Previously, we proposed the outer-hair-cell-specific protein prestin, as a possible biomarker and provided proof of concept in noise- and cisplatin-induced hearing loss. Our ototoxicity data suggest that circulatory prestin changes after inner ear injury are not static and that there is a temporal pattern of change that needs to be further characterized before practical information can be extracted. To achieve this goal, we set out to 1) describe the time course of change in prestin after intense noise exposure, and 2) determine if the temporal patterns and prestin levels are sensitive to severity of injury. After assessing auditory brainstem thresholds and distortion product otoacoustic emission levels, rats were exposed to intense octave band noise for 2 h at either 110 or 120 dB SPL. Auditory function was re-assessed 1 and 14 days later. Blood samples were collected at baseline, 4, 24, 48, 72 h and 7 and 14 days post exposure and prestin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Functional measures showed temporary hearing loss 1 day after exposure in the 110 dB SPL group, but permanent loss through Day 14 in the 120 dB SPL group. Prestin levels temporarily increased 5% at 4 h after 120 dB SPL exposure, but not in the 110 dB SPL group. There was a gradual decline in prestin levels in both groups thereafter, with prestin being below baseline on Day 14 by 5% in the 110 dB group (NS) and more than 10% in the 120 dB SPL group (p = 0.043). These results suggest that there is a temporal pattern of change in serum prestin level after noise-induced hearing loss that is related to severity of hearing loss. Circulatory levels of prestin may be able to act as surrogate biomarker for hearing loss involving OHC loss.

Utilizing prestin as a predictive marker for the early detection of outer hair cell damage.

PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system. RESULTS: The mean serum prestin levels were 377.0 ±â€¯135.3, 411.3 ±â€¯73.1, 512.6 ±â€¯106.0, 455.0 ±â€¯74.2 and 555.3 ±â€¯47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p < 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p < 0.05). CONCLUSIONS: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.