Autoimmune Disease of the Inner Ear Workup

Updated: Sep 27, 2018
  • Author: Neeraj N Mathur, MBBS, MS, DNB(ENT), MNAMS, FAMS; Chief Editor: Arlen D Meyers, MD, MBA  more...
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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. [15]

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%. [16]

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. [16]

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. [17] 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). [18] 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. [19] 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. [20] 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.