The role of alpha-1-antitrypsin levels in perilymph in relation to the etiology of patients with inner ear hearing loss

Introduction: The highly sensitive cellular structures in the inner ear are vulnerable to manifold influences like inflammation, disease-specific molecular changes, and aging leading to damaging processes and as a consequence of this to sensorineural hearing loss (SNHL). In our previous studies proteome analysis of the inner ear fluid perilymph showed disease-specific differences in the level and occurrence of perilymph proteins [1] and a correlation between alpha-1-antitrypsin protein levels and the severity of hearing loss [2]. Therefore, in this study, we focused on the role of alpha-1-antitrypsin (AAT), a circulating glycoprotein with tissue protection function, in human perilymph.

Methods: Perilymph samples of patients with SNHL undergoing cochlear implantation surgeries were analyzed by mass spectrometry coupled with liquid chromatography (LC-MS) by a shotgun proteomics approach. Max Quant software was used for protein identification and relative quantification.

Results: In perilymph samples of patients suffering from different diseases leading to SNHL we identified clearly de- or increased levels of the protein AAT in the different patient groups.

Conclusion: This in-depth proteome analysis of human perilymph paves the way for understanding the role of AAT and provides evidence for a potential role of AAT therapy in the prevention, or possibly reversal, of some inner ear pathologies.

[1] Schmitt et al. ACS Omega 2021, 6, 21241−21254

[2] El-Saied S et al. Clin Otolaryngol. 2020 Jul;45(4):495-499

This work was supported by the DFG Cluster of Excellence EXC 2177/1 "Hearing4all".

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