Date Published: October 17, 2014
Publisher: Public Library of Science
Author(s): Sung Huhn Kim, Jin Young Kim, Hyun Jin Lee, Mia Gi, Bo Gyung Kim, Jae Young Choi, Bernd Sokolowski.
Meniere’s disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere’s disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere’s disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere’s disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere’s disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23–48 kDa and 63–75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere’s disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient’s serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere’s disease.
In 1861, Prosper Meniere first described Meniere’s disease as an inner ear disorder that manifests as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. The prevalence of Meniere’s disease is 3.5–513 per 100,000, which is higher than the prevalence of systemic lupus erythematosus (SLE) and multiple sclerosis . The unpredictable nature of Meniere’s disease has a serious effect on patients’ daily life. During active episodes, the quality of life score of patients with Meniere’s disease is thought to be lower than that of AIDS patients treated with AZT, that of patients with severe chronic obstructive pulmonary disease, and that of non-institutionalized patients with Alzheimer’s disease . The main pathologic site is thought to be the inner ear, which consists of the cochlea, vestibule, and endolymphatic sac. A characteristic finding of Meniere’s disease is the dilatation of the endolymphatic compartment of the inner ear caused by an increase in endolymph (endolymphatic hydrops, Fig. 1) . The proposed etiologies of endolymphatic hydrops are autoimmune, allergic, genetic, traumatic, and infectious (viral) –. These finally result in endolymphatic hydrops by deteriorating ion homeostasis and fluid volume regulation in the inner ear . However, the exact pathologic mechanism underlying endolymphatic hydrops is still unknown.
The pathophysiology of Meniere’s disease is still unknown, and various etiologies have been proposed. One of the proposed etiologies of Meniere’s disease is autoimmunity; this putative etiology is supported by the fact that this disease often occurs bilaterally (in 25–40% of patients), responds to glucocorticoids and anti-inflammatory treatments, and is characterized by elevated levels of autoantibodies or circulating immune complexes and antigen-antibody reactions between patient serum and animal inner ear tissues . However, Meniere’s disease does not always occur bilaterally, and experimental studies have only been performed on small numbers of patients or have only targeted a restricted number of autoantibodies or inflammatory markers.
The findings of this study suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere’s disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient’s serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere’s disease. Further studies with mass screening using candidate antigen-antibody reactions are needed to identify future treatment modalities and to determine the true prevalence of autoimmune pathologic mechanisms underlying Meniere’s disease.