Immune Mediated Ear Disease/Hearing Loss

National Institute on Deafness and Other Communication Disorders (NIDCD) convened a workshop at the Hyatt Regency Bethesda in Bethesda, MD, titled Immune-Mediated Ear Disease/Hearing Loss. The goals of the workshop were to obtain updates on the current status of immune-mediated ear disease research; to identify research gaps, and to get expert recommendations regarding research needs that will aid our understanding of this complex form of hearing loss, and ultimately lead to diagnostics and therapies that preserve natural hearing. For this workshop, immune-mediated ear disease was defined to include both primary autoimmune sensorineural hearing loss (NHL) originating in the inner ear and secondary immune-mediated ear disease/hearing loss (IMED) from systemic immune/autoimmune disease originating outside the inner ear.

The workshop was chaired by Dennis R. Trune, Ph.D., of the Oregon Health & Science University. Dr. Trune moderated the sessions and discussion. The workshop panel consisted of 10 basic scientists and clinician-scientists with expertise in the areas of autoimmunity, immunology, otolaryngology, genetics, and infectious disease. Both academic and industry perspectives were represented. In addition, interested members of the public attended and commented.

The meeting began at 8:30 a.m., with opening remarks from NIDCD Deputy Director Judith A. Cooper, Ph.D. The workshop organizer, Bracie Watson, Jr., Ph.D., NIDCD, then gave background remarks regarding the rationale and need for the workshop. He emphasized that the workshop discussion and research recommendations should be limited only to the science and should not involve any discussion of potential initiatives that might arise from the workshop. Each panelist was allocated 30 minutes for his or her presentation, followed by a brief question and answer session. Presentations were clustered by topic area; at the end of each cluster was a 30-minute discussion period. On day two, following the last presentation, there was a general discussion, followed by research recommendations provided by the panel members. The workshop adjourned at noon.

Recommendations resulting from the workshop have been aggregated into seven categories listed below:

Research Recommendations

  1. Clinical diagnostics, etiology, and patient populations
    • The development of clinical diagnostic criteria for IMED is critical. The criteria should not include a specific immune test or a response to therapy. This is a precursor to the collection of population data and to evaluating the efficacy of any therapy.
    • Identify the contribution, risk, and mechanisms of systemic vs. non-systemic ASNHL, including studies of the role of low-level autoimmunity in long-standing diseases, e.g., rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).
    • Development of better sub-group classification of IMED.
    • Investigations of hearing loss associated with the presence of systemic autoimmune disease, e.g., SLE, RA.
    • Blinded clinical trials and clinical studies to establish treatment guidelines.
    • Evaluation of gender differences in ASNHL susceptibility as well as the role of hormones, pregnancy, and menses about threshold fluctuations.
    • Epidemiologic studies of IMED.
  2. Laboratory diagnostics/biomarkers
    • Identification of IMED-associated antibodies for use as a diagnostic test.
    • Development of IMED diagnostic tests with better sensitivity and specificity.
    • Identification of disease associations with antigens/antibodies that have positive predictive (diagnostic) value.
    • Investigation and specification of the histopathology of IMED.
  3. Immunology studies
    • The role of the innate immune system in ASNHL.
    • Adaptive immune response in the ear over time.
    • The transition from innate to adaptive immune responses in IMED.
    • Identification of T- or B- cells ‘particular’ to the inner ear in animal models.
    • Profiles of T-cells in the ear using animal models.
    • Characterization of inner ear-specific immune responses in normal and ASNHL individuals.
    • The role of the endolymphatic sac in IMED and ASNHL.
  4. Cellular/inflammatory mechanisms
    • Identification of the presence and characteristics of resident inflammatory cells in the inner ear.
    • Investigation of systemic inflammatory processes and identification of biomarkers.
    • Identification of target antigens and determination of whether this antigen is a cause or consequence.
    • Studies to understand the inner ear immune response as an organ-specific immune system.
    • Investigation of the repair processes of the cochlea after the immune-mediated cochlear attack, as well as an understanding of the mechanisms of steroid treatment and responsiveness.
    • The role of the vasculature, ionic imbalance, and inflammatory processes in the etiology of IMED and identification of associated/concurrent autoimmune responses.
    • Studies to differentiate the immune suppressive mechanisms of steroid treatment/responsiveness from other steroid-induced cellular processes.
  5. Genetic studies
    • Genome-Wide Association Studies (GWAS), twin studies, association studies targeting human leukocyte antigens (HLA), and collection of exposure data/environmental factors to assess gene-environment interactions.
    • Transcriptome analyses of human cochlear cells of ASNHL patients vs. unaffected patients.
  6. The role of cytomegalovirus (CMV) and other viruses in IMED
    • Determination of the prevalence of CMV antibodies in the sera of ASNHL patients.
    • Investigation of the role of latent CMV in the etiology of adult ASNHL and whether reactivation of latent virus occurs.
    • Evaluation of the use of antivirals to treat ASNHL patients.
    • Studies of the endolymphatic sac as a target of viruses.
  7. Research resource needs
    • Creation of an ASNHL registry, possibly in collaboration with support groups.
    • Establishment of research collaborations to encourage new investigators, patient referrals, and donations of temporal bones of individuals with NHL. Possible collaborations could include autoimmune disorder support groups, organizations such as the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), private practice physicians, and physicians from specialties outside otolaryngology, e.g., rheumatologists.
    • True estimates of the incidence and prevalence of ASNHL are presently unknown. Clinical, basic, and epidemiologic studies of ASNHL would benefit from the inclusion of study populations and international Principal Investigators/Researchers.
    • Creation of a tissue bank including blood, serum, endolymphatic sacs, saliva, buccal swabs, and DNA.
    • Development of better animal models, which may include zebrafish.
    • Development of cell lines of the spiral ligament and endolymphatic sac.



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4 Davis, A, Smith, P, Ferguson, M, Stephens, D, and Gianopoulos, I, (2007). Acceptability, Benefit, and Costs of Early Screening for Hearing Disability: A Study of Potential Screening Tests and Models. Health Technol Assess. Oct; 11(42): 1-294.

5 Senate Report 110-410, page 111, Report of the Committee on Appropriations, U.S. Senate, on S. 3230 (making appropriations to the Departments of Labor, Health and Human Services, and Education, and Related Agencies Appropriation Bill, 2009).




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10  Source for the second statistic is no longer available online (verified January 2019).

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16 US Census Bureau figures; link no longer available.

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22 Davis, A, Smith, P, Ferguson, M, Stephens, D, and Gianopoulos, I, (2007). Acceptability, Benefit, and Costs of Early Screening for Hearing Disability: A Study of Potential Screening Tests and Models. Health Technol Assess. Oct; 11(42): 1-294.

23 Estimated from Davis, A, Smith, P, Ferguson, M, Stephens, D, and Gianopoulos, I, (2007). Acceptability, Benefit, and Costs of Early Screening for Hearing Disability: A Study of Potential Screening Tests and Models. Health Technol Assess. Oct; 11(42): 1-294; Personal communication, Howard Weinstein, August 2009.


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