Autoimmune Inner Ear Disease (AIED) is a poorly characterized disease that is difficult to diagnose and treat because of the inability to identify a common biomarker/mechanism of disease. Incidence and prevalence of this disorder cannot be accurately determined, because of the inability to make a definitive diagnosis. Patients are initially treated with systemic steroids;however, a large percentage of initial responders become refractory over time, due an unknown mechanism. Fortunately, for those patients whose disease progression and subsequent hearing loss cannot be prevented, a cochlear implant can provide hearing to the deafened AIED patient. We have identified a decoy receptor to be a novel biomarker for Autoimmune Inner Ear Disease (AIED). This molecular decoy receptor serves as a trap to bind inflammatory proteins without the subsequent signaling events, thus suppressing an inflammatory response. We have observed that this decoy receptor is minimally induced in peripheral blood mononuclear cells (PBMC) exposed to autologous perilymph in patients with AIED, as compared to controls undergoing cochlear implant surgery (p<0.05). Furthermore, we have preliminary evidence that pretreatment decoy receptor levels in the peripheral blood can predict the clinical response to steroid therapy in AIED patients, as measured by audiometric improvement (p<0.0001). This has led us to the following hypothesis: Patients with AIED do not maintain the immunoprivileged status of the cochlea because they are unable to express the decoy receptor in response to antigenic stimuli. This leads to immune mediated inner ear inflammation resulting in progressive sensorineural hearing loss. We further hypothesize that this decoy receptor is a novel marker of steroid responsive hearing loss in patients with AIED. This hypothesis will be tested through three specific aims:
Aim 1 : Determine if a favorable response to steroid therapy in presumptive AIED patients with sudden declines in hearing correlates with the ability to increase decoy receptor expression.
Aim 2 : Determine if single nucleotide polymorphisms (SNPs) of key inflammatory genes and/or HLA genes predict the outcome of steroid response in AIED.
Aim 3 : Determine if the failure of decoy receptor expression in PBMC from AIED patients in response to perilymph is due to differences in perilymph composition, or a result of altered PBMC responses to common perilymph molecules. We have identified a potential biologic marker for Autoimmune Inner Ear Disease (AIED) that can predict steroid response. The ability to predict steroid response would: (1) aid in development of a diagnostic test for AIED, (2) better predict which patients would respond to steroids thereby avoiding undue risk associated with administration of steroids for those who are expected not to respond, and (3) provide a rationale for development of novel therapies.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Auditory System Study Section (AUD)
Program Officer
Watson, Bracie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Feinstein Institute for Medical Research
United States
Zip Code
Pathak, Shresh; Hatam, Lynda J; Bonagura, Vincent et al. (2013) Innate immune recognition of molds and homology to the inner ear protein, cochlin, in patients with autoimmune inner ear disease. J Clin Immunol 33:1204-15
Svrakic, Maja; Pathak, Shresh; Goldofsky, Eliot et al. (2012) Diagnostic and prognostic utility of measuring tumor necrosis factor in the peripheral circulation of patients with immune-mediated sensorineural hearing loss. Arch Otolaryngol Head Neck Surg 138:1052-8
Pathak, Shresh; Goldofsky, Elliot; Vivas, Esther X et al. (2011) IL-1? is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J Immunol 186:1870-9