Abstract
Objective: Etiologies for Ménière’s disease and sudden sensorineural hearing loss remain unknown. Indirect evidence exists for allergy-mediated or autoimmune process. The purpose of this study is to determine whether immunogenic proteins share similar sequences with inner ear proteins, which may lead to cross-reactivity and immune activation in inner ear disorders.
Method: Comprehensive bioinformatic primary sequence analyses of intact and mutated proteins associated with human syndromic and nonsyndromic hearing loss and proteins expressed in the human inner ear was performed. Comparison of sequences to epitopes in the Immune Epitope Database was performed by exact match, BLAST, and BLOSUM62 score computational algorithms.
Results: Computational analysis of primary protein sequence for 81 known inner ear proteins, 102 proteins from genes identified in syndromic and non-syndromic hearing loss, and 438 protein sequences with known mutations that contribute to sensorineural hearing loss was compared to 151,086 epitopes previously implicated in allergic, autoimmune, and infectious disorders within the Immune Epitope Database. The exact match and BLAST algorithms identified 1925 and 97 unique epitope matches, respectively. Top BLOSUM62 score algorithm resulted in a single hit for the 47 kDa membrane antigen. Other epitopes included those seen in allergic rhinitis, infectious diseases, and autoimmune disorders.
Conclusion: Abnormal immune activation is suspected in Ménière’s disease and SSNHL. Candidate immune epitopes were identified that may contribute to pathogenesis of these disorders. While these epitopes await clinical validation, they present novel targets for diagnosis and treatment of sensorineural hearing loss.
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