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Autoimmune Disease of the Inner Ear Workup

  • Author: Neeraj N Mathur, MBBS, MS; Chief Editor: Arlen D Meyers, MD, MBA  more...
Updated: Mar 04, 2016

Laboratory Studies

Antigen-nonspecific tests are useful in routine screening for evidence of systemic immunologic dysfunction, yet specifically are not known to correlate with a diagnosis of immune-mediated inner ear disease. Antigen-nonspecific tests are as follows:

  • Levels of circulating immune complexes
  • Complement levels (C3, C4)
  • Antinuclear antibody levels
  • Rheumatoid factor
  • Acute phase reactants - Erythrocyte sedimentation rate, C-reactive protein

A study by Dayal et al discovered that patients with autoimmune ear disease having no systemic autoimmune illness often show high levels of antinuclear antibodies (with a speckled pattern) and also sometimes have high levels of rheumatoid factor. The positive yield of other detailed tests was low.[8]

A study by Svrakic et al indicated that tumor necrosis factor (TNF) levels can be used diagnostically and prognostically in immune-mediated inner ear disease. The study, which involved 85 patients with clinical and audiometric characteristics of immune-mediated SNHL, as well as 11 controls, found that patients with immune-mediated SNHL who were nonresponsive to steroids had a higher mean baseline plasma level of TNF (27.6 pg/mL), as derived from peripheral venous blood, than did those who were responsive to steroids (24.1 pg/mL), and that both had higher TNF levels than did the controls (14.4 pg/mL). According to the investigators, a baseline plasma TNF level of more than 18.8 pg/mL from the peripheral circulation has a positive predictive value for immune-mediated SNHL of more than 97%.[9]

Svrakic and colleagues also found evidence that in non-steroid-responsive patients with immune-mediated SNHL, peripheral blood mononuclear cells (PBMCs) respond differently to in vitro stimulation with dexamethasone than do those of steroid-responsive patients, with the mean TNF level secreted by the PBMCs slightly increasing (from 11.2 pg/mL to 11.7 pg/mL) with stimulation instead of decreasing.[9]

Antigen-specific tests are as follows:

  • Migration inhibition assay: The patient's lymphocytes are placed in a capillary tube with serum containing inner ear antigens present on one end. If the patient's lymphocytes previously have been sensitized to the inner ear antigen, migration inhibition factor is released and impedes dispersion of lymphocytes from the tube. This assay is a gross test of immune reactivity.
  • Lymphocyte transformation test (LTT): The LTT measures the response of the patient's sensitized lymphocytes to known inner ear antigens. The patient's lymphocytes are exposed to serum containing inner ear antigens. A proliferative response occurs and is compared to that of known negative control lymphocytes. Measurement is made by recording the incorporation of tritiated thymidine into new DNA as cell synthesis occurs. Sensitivity of the LTT is reported to be 50-80% when symptoms are active in an immunocompetent patient.
  • Western blot analysis for antibodies to inner ear antigen
    • Harris and Sharp used bovine inner ear extract as antigen in Western blot assays and detected antibody to a 68-kd inner ear antigen in 19 of 54 patients (35%) with progressive SNHL. Recent update includes a cohort of 279 patients with rapidly progressive SNHL, of whom 90 (32%) had positive results of Western blot analysis for the 68-kd antibody.
    • Animals with experimentally induced SNHL possessed autoantibodies to the identical component of the inner ear antigenic isotope to which patients' sera reacted.
    • Moscicki et al confirmed the finding of circulating antibodies against a 68-kd protein, which was found in 42 of 72 patients (58%) with IPBSNHL.[10] Patients with positive test results for the antibody were more likely than those with negative results to have hearing loss that responded to steroid treatment (75% vs 18%). This study is the first to show a correlation between Western blot 68-kd positivity and steroid responsiveness.
    • Rauch subsequently identified the 68-kd protein as heat shock protein 70 (HSP 70).[11] Heat shock proteins are constitutively produced by host and pathogens and usually are up-regulated in response to infection or other stresses.
    • Antibodies to HSP 70 were detected in 47% of 30 patients with Ménière disease, thus identifying a subset of patients with Ménière disease with an immune basis for their symptoms.
    • The LTT and Western blot immunoassay must be performed in specialized immunology laboratories, often on a send-out basis.
    • Control populations vary from persons with normal hearing to those with systemic autoimmune diseases. The 68-kd positivity in these control populations averages 5%. This specificity of approximately 95% appears fairly high but is rather insensitive when used in the general population.
    • Gong et al found that 2 subcomponents of crude inner ear antigen (the 31 kD protein and the 60 kD protein) may induce autoimmune inner ear disease independently in the guinea pig cochlea.[12] The 31 kD protein may correspond to the 30 kD protein identified by Cao et al as myelin protein zero (P0), which is derived from the acoustic nerve and spiral ganglion.[13] The 31 kD protein may be of use in the future for early diagnosis of autoimmune inner ear disease (AIED).

Histologic Findings

Histopathologic human temporal bone studies of patients with immune-mediated inner ear disease rarely are reported in the literature. Further studies may help elucidate the pathophysiology involved in this condition.

Contributor Information and Disclosures

Neeraj N Mathur, MBBS, MS Director-Professor, Department of ENT and Head Neck Surgery, Vardhman Mahavir Medical College and Associated Safdarjang Hospital; Professor, Delhi University and Indraprastha University, India

Neeraj N Mathur, MBBS, MS is a member of the following medical societies: Royal Society of Medicine, Indian Medical Association, Association of Otolaryngologists of India, Cochlear Implant Group of India, National Academy of Medical Sciences (India), Neuro-Otological and Equilibriometric Society of India

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Peter S Roland, MD Professor, Department of Neurological Surgery, Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, Director, Clinical Center for Auditory, Vestibular, and Facial Nerve Disorders, Chief of Pediatric Otology, University of Texas Southwestern Medical Center; Chief of Pediatric Otology, Children’s Medical Center of Dallas; President of Medical Staff, Parkland Memorial Hospital; Adjunct Professor of Communicative Disorders, School of Behavioral and Brain Sciences, Chief of Medical Service, Callier Center for Communicative Disorders, University of Texas School of Human Development

Peter S Roland, MD is a member of the following medical societies: Alpha Omega Alpha, American Auditory Society, The Triological Society, North American Skull Base Society, Society of University Otolaryngologists-Head and Neck Surgeons, American Neurotology Society, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Otological Society

Disclosure: Received honoraria from Alcon Labs for consulting; Received honoraria from Advanced Bionics for board membership; Received honoraria from Cochlear Corp for board membership; Received travel grants from Med El Corp for consulting.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

Robert A Battista, MD, FACS Assistant Professor of Otolaryngology, Northwestern University, The Feinberg School of Medicine; Physician, Ear Institute of Chicago, LLC

Robert A Battista, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, Illinois State Medical Society, American Neurotology Society, American College of Surgeons

Disclosure: Nothing to disclose.


The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous authors Shelley Jaquish, MD, and William L Meyerhoff, MD, PhD, to the development and writing of this article.

  1. Goodall AF, Siddiq MA. Current understanding of the pathogenesis of autoimmune inner ear disease: a review. Clin Otolaryngol. 2015 Oct. 40 (5):412-9. [Medline].

  2. Lobo DR, García-Berrocal JR, Ramírez-Camacho R. New prospects in the diagnosis and treatment of immune-mediated inner ear disease. World J Methodol. 2014 Jun 26. 4 (2):91-8. [Medline]. [Full Text].

  3. Hughes GB, Barna BP, Calarese LH. Immunologic Disorders of the Inner Ear. Bailey BJ, ed. Head and Neck Surgery-Otolaryngology. Philadelphia, Pa: Lippincott; 1993. 1833-1842.

  4. Berlinger NT. Meniere's disease: new concepts, new treatments. Minn Med. 2011 Nov. 94(11):33-6. [Medline].

  5. Huang NC, Sataloff RT. Autoimmune inner ear disease in children. Otol Neurotol. 2011 Feb. 32(2):213-6. [Medline].

  6. Yoo TJ, Tomoda K, Stuart JM, Cremer MA, Townes AS, Kang AH. Type II collagen-induced autoimmune sensorineural hearing loss and vestibular dysfunction in rats. Ann Otol Rhinol Laryngol. 1983 May-Jun. 92(3 Pt 1):267-71. [Medline].

  7. Harris JP, Sharp PA. Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. Laryngoscope. 1990 May. 100(5):516-24. [Medline].

  8. Dayal VS, Ellman M, Sweiss N. Autoimmune inner ear disease: clinical and laboratory findings and treatment outcome. J Otolaryngol Head Neck Surg. 2008 Aug. 37(4):591-6. [Medline].

  9. Svrakic M, Pathak S, Goldofsky E, et al. 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. 2012 Nov. 138(11):1052-8. [Medline].

  10. Moscicki RA, San Martin JE, Quintero CH, Rauch SD, Nadol JB Jr, Bloch KJ. Serum antibody to inner ear proteins in patients with progressive hearing loss. Correlation with disease activity and response to corticosteroid treatment. JAMA. 1994 Aug 24-31. 272(8):611-6. [Medline].

  11. Rauch SD, San Martin JE, Moscicki RA, Bloch KJ. Serum antibodies against heat shock protein 70 in Menière's disease. Am J Otol. 1995 Sep. 16(5):648-52. [Medline].

  12. Gong SS, Yu DZ, Wang JB. Relationship between three inner ear antigens with different molecular weights and autoimmune inner ear disease. Acta Otolaryngol. 2002 Jan. 122(1):5-9. [Medline].

  13. Cao MY, Deggouj N, Gersdorff M, Tomasi JP. Guinea pig inner ear antigens: extraction and application to the study of human autoimmune inner ear disease. Laryngoscope. 1996 Feb. 106(2 Pt 1):207-12. [Medline].

  14. Pathak S, Goldofsky E, Vivas EX, Bonagura VR, Vambutas A. IL-1ß is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J Immunol. 2011 Feb 1. 186(3):1870-9. [Medline]. [Full Text].

  15. McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1979 Sep-Oct. 88(5 Pt 1):585-9. [Medline].

  16. Sismanis A, Thompson T, Willis HE. Methotrexate therapy for autoimmune hearing loss: a preliminary report. Laryngoscope. 1994 Aug. 104(8 Pt 1):932-4. [Medline].

  17. Harris JP, Weisman MH, Derebery JM, et al. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA. 2003 Oct 8. 290(14):1875-83. [Medline].

  18. Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol. 2005 Sep. 26(5):903-7. [Medline].

  19. Matteson EL, Choi HK, Poe DS, et al. Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center, open-label, pilot study. Arthritis Rheum. 2005 Jun 15. 53(3):337-42. [Medline].

  20. Pathak S, Stern C, Vambutas A. N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients. Immunol Res. 2015 Dec. 63 (1-3):236-45. [Medline].

  21. Luetje CM. Theoretical and practical implications for plasmapheresis in autoimmune inner ear disease. Laryngoscope. 1989 Nov. 99(11):1137-46. [Medline].

  22. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope. 1999 Jul. 109(7 Pt 2):1-17. [Medline].

  23. Silverstein H. Use of a new device, the MicroWick, to deliver medication to the inner ear. Ear Nose Throat J. 1999 Aug. 78(8):595-8, 600. [Medline].

  24. Swan EE, Mescher MJ, Sewell WF, Tao SL, Borenstein JT. Inner ear drug delivery for auditory applications. Adv Drug Deliv Rev. 2008 Dec 14. 60(15):1583-99. [Medline]. [Full Text].

  25. Hamid M, Trune D. Issues, indications, and controversies regarding intratympanic steroid perfusion. Curr Opin Otolaryngol Head Neck Surg. 2008 Oct. 16(5):434-40. [Medline]. [Full Text].

  26. Haynes DS, O'Malley M, Cohen S, Watford K, Labadie RF. Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy. Laryngoscope. 2007 Jan. 117(1):3-15. [Medline].

  27. Broughton SS, Meyerhoff WE, Cohen SB. Immune-mediated inner ear disease: 10-year experience. Semin Arthritis Rheum. 2004 Oct. 34(2):544-8. [Medline].

Inner ear.
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