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Migraine (MI) is the most common neurological disease, affecting with 20% of the world population. A subset of 25% of MI patients showcase concurrent vestibular symptoms, which may classify as vestibular migraine (VM). Meniere's disease (MD) is a complex inner ear disorder defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss with a significant autoimmune/autoinflammatory contribution, which symptoms overlap with VM. Blood samples from 18 patients with MI (5), VM (5) and MD (8) and 6 controls were collected and compared in a case-control study. Droplet-isolated nuclei from mononuclear cells used to generate scRNAseq and scATACseq data sets from MI, VM and MD. MI and VM have no differences in their immune transcriptome; therefore, they were considered as a single cluster for further analyses. Natural Killer (NK) cells transcriptomic data support a polarisation triggered by Type 1 innate immune cells via the release of interleukin (IL)-12, IL-15 and IL-18. According to the monocyte scRNAseq data, there were two MD clusters, one inactive and one driven by monocytes. The unique pathways of the MI + VM cluster were cellular responses to metal ions, whereas MD monocyte-driven cluster pathways showed responses to biotic stimuli. MI and MD have different immune responses. These findings support that MI and VM have a Type 1 immune lymphoid cell response, and that there are two clusters of MD patients, one inactive and one Monocyte-driven., (© 2024 The Author(s). Immunology published by John Wiley & Sons Ltd.)

Objectives: Previous studies have highlighted associations between certain inflammatory cytokines and Ménière's Disease (MD), such as interleukin (IL) -13 and IL-1β. This Mendelian randomization aims to comprehensively evaluate the causal relationships between 91 inflammatory cytokines and MD., Methods: A comprehensive two-sample Mendelian randomization (MR) analysis was conducted to determine the causal association between inflammatory cytokines and MD. Utilizing publicly accessible genetic datasets, we explored causal links between 91 inflammatory cytokines and MD risk. Comprehensive sensitivity analyses were employed to assess the robustness, heterogeneity, and presence of horizontal pleiotropy in our findings., Results: Our findings indicate that MD causally influences the levels of two cytokine types: IL-10 (P=0.048, OR=0.945, 95%CI =0.894~1.000) and Neurotrophin-3 (P=0.045, OR=0954, 95%CI =0.910~0.999). Furthermore, three cytokines exhibited significant causal effects on MD: CD40L receptor (P=0.008, OR=0.865, 95%CI =0.777-0.963), Delta and Notch-like epidermal growth factor-related receptor (DNER) (P=0.010, OR=1.216, 95%CI =1.048-1.412), and STAM binding protein (P=0.044, OR=0.776, 95%CI =0.606-0.993)., Conclusion: This study suggests that the CD40L receptor, DNER, and STAM binding protein could potentially serve as upstream determinants of MD. Furthermore, our results imply that when MD is regarded as the exposure variable in MR analysis, it may causally correlate with elevated levels of IL-10 and Neurotrophin-3. Using these cytokines for MD diagnosis or as potential therapeutic targets holds great clinical significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Zhang, Tang and Dai.)

Meniere' s disease is a clinical syndrome that consists of episodes of spontaneous vertigo usually associated with unilateral fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The pathogenesis remains unknown, and the underlying pathophysiologic state in Meniere' s disease is endolymphatic hydrops. Allergy is thought to be one of the etiologic factors. The present study examined whether subjects with Meniere' s disease have pathological immune reaction related to type Ⅰ allergy., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Platelet rich plasma procedure (PRP) is considered to be one of the safest aesthetic procedures. Adverse reactions after PRP administration are extreme rare., Purpose: We present the patient with serum sickness disease (SSD) after PRP procedure., Objective and Methods: 41 years old female suffers from alopecia areata for 5 years with frequent relapses and she has been suffering from Menier's disease recurrent symptoms for 6 years. The patient developed SSD after third PRP rejuvenating procedure and she has also noticed new alopecia areata lesions, but without Menier's disease symptoms. After SSD, 4 months later, she developed severe symptoms of Menier's disease with an episode of sudden sensorineural hearing loss. It alleviated only after intravenous administration of methylprednisolone. In our opinion, significant contraindication of PRP procedure is an autoimmune disease in the active phase., (© 2018 Wiley Periodicals, Inc.)

Inner ear disease is characterized by tinnitus, deafness and vertigo. The pathogenesis remains unknown. In the past, it is considered to be related to vascular disease such as thrombus and hemadostenosis.However, more and more researches indicate that it may be associated with multiple factors mediated by allergy. This paper reviews some possible pathogenesis of Meniere disease, including type Ⅰ allergy, autoimmunity, circulating immune complex and immune genetic.

In an attempt to develop an animal model of immune mediated Meniere's disease, we have injected lipopolysaccharide (LPS) directly into scala media of guinea pigs and monitored functional and morphological changes over a period of 6 weeks. Depending on the concentration of LPS, changes ranged from moderate-to-severe hearing loss and endolymphatic hydrops with minimal cellular infiltrate or fibrosis, to dense cellular infiltration that filled the scalae. Interestingly, higher concentrations of LPS not only induced severe cellular infiltration, hydrops, and hearing loss, but also a substantial enlargement of the endolymphatic duct and sac. Moreover, LPS injections into perilymph failed to induce hydrops, yet still resulted in cellular infiltration and fibrosis in the cochlea. This suggests that chronic hydrops resulting from an immune challenge of the cochlea may not be due to blockage of the endolymphatic duct and sac, restricting fluid absorption. Furthermore, injecting antigen into endolymph may produce chronic immune-mediated hydrops, and provide a more promising animal model of Meniere's, although animals did not display signs of vestibular dysfunction, and the hearing loss was relatively severe., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

The role of immunological factors in the pathophysiology of Meniere's disease (MD) has been hypothesized. In order to evaluate the current level of evidence on autoimmunity in MD, original articles relevant to the matter (1970-2016) were reviewed. The following has been considered to support the theory of autoimmunity in MD (1) the increased prevalence of autoimmune diseases among MD patients, (2) the elevated levels of antibodies and immunocomplexes in MD patients, (3) the association of MD with HLA-types and genetic polymorphisms and (4) the positive corticosteroid-responsiveness detected in some MD patients. However, all studies have been small and lack positive replication. Studies concerning antibodies, HLA types and genetic polymorphisms have produced conflicting results and no single antibody, HLA type or polymorphism has been found in all or even in a significant subpopulation of MD patients. No convincing basic research evidence of autoimmunity in MD exists hence the field needs further study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To date, the pathogenesis of Ménière's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system-related genes and sporadic MD. The whole RNA-sequencing (RNA-seq) technology was used to analyse the transcriptome of peripheral blood mononuclear cells of three MD patients and three control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log 2 fold change| > 1 and P < 0·05). Gene ontology (GO) enrichment analysis illustrated that immune relevant factors played a key role in the pathogenesis of MD. Of 366 DEGs, we focused upon analysing the possible immune-related genes, among which the significantly up-regulated genes [glutathione S-transferase mu 1 (GSTM1), transmembrane protein 176 (TMEM176)B, TMEM176A] and down-regulated genes [solute carrier family 4 member (SLC4A)10 and SLC4A1] especially drew our attention. The mRNA expression levels of GSTM1, TMEM176B, TMEM176A, SLC4A1 and SLC4A10 were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The serum concentration of GSTM1, TMEM176B and SLC4A10 proteins were measured by enzyme-linked immunosorbent assay (ELISA). Considering the results of qRT-PCR and ELISA, it was noteworthy that GSTM1 exhibited the highest fold change between two groups, which was consistent with the deep sequencing results by RNA-seq. In conclusion, our study first offers a new perspective in MD development on the basis of RNA expression patterns, suggesting that immune factors might be involved in the MD pathogenesis. Remarkably, GSTM1 might be a possible candidate gene for the diagnostic biomarker of MD and provides the basis for further biological and functional investigations., (© 2017 British Society for Immunology.)

Objective: Since 1930, dietary modification has been proposed as adjunct treatment in Ménière's disease (MD) with different and controversial results. We report the case of a 42-year-old female suffering from definite MD and intermittent seasonal allergic rhino-conjunctivitis because it highlights the importance of evaluating the different combinations of defined causative elements in an atopic patient with MD., Methods: An immunological and audiological evaluation was performed, including pure-tone, speech, and immittance audiometry; glycerol dehydration test; bithermal caloric testing; video head impulse test; cervical vestibular evoked myogenic potentials; static posturography; and Dizziness Handicap Inventory questionnaire., Results: A milk-free diet was crucial to relief from MD symptoms and a cow's milk challenge test was able to evoke them but vestibukar symptoms persist., Conclusions: The effect of dietary modification was evident only after specific immunotherapies against other allergens. This highlights the importance of evaluating different combinations of defined causative elements in the allergic treatment of MD.

Objective: The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction., Methods: We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders., Results: Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV., Conclusion: The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated., Abbreviations: AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T 4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

Objective: To evaluate the correlation between type Ⅰ allergic reaction and pathogenesis of Meniere's disease. Methods: A total of 35 (10 male vs. 25 female) patients aged between 21-66 years diagnosed with Meniere's disease were recruited to this study, mean age of them was (47.3±13.6) years. The control group consisted of 15 inpatients (5 male vs. 10 female) with pharyngolaryngeal diseases but without otologic and rhinologic abnormity, mean age was 45.4±12.8 years. Allergic prevalence, serous total immunoglobulin E( tIgE ) levels, serous specific immunoglobulin E( sIgE ) levels and subtypes of T lymphocytes were measured and compared in patients with Meniere's disease and the control group. Severity of vertigo, tinnitus and sensation of fullness were compared between Meniere ' s disease patients with or without allergy. Results: Allergic prevalence were significantly different ( Pearson chi - square 5.832, P <0.05) between patients with Meniere ' s disease and the control group(57.1% vs . 20.0%). Patients with Meniere's disease report higher level of serous tIgE compared with controls, the difference is statistically significant ( Z =168.000, P <0.05). However, positive rates of sIgE of food allergens and inhalant allergens were not significantly different between patients with Meniere's disease and the control group. Scores of vertiginous severity, dizziness handicap inventory (DHI) and tinnitus handicap inventory (THI) were significantly different between Meniere's disease patients with or without allergy ( P <0.05). Treg and Treg/Th17 levels ( Z =26.000) were much higher in Meniere's disease patients with allergy than in the controls( P <0.05). Conclusions: Patients with Meniere's disease report higher rate of allergy than the control group. Type Ⅰ allergic reaction is thought to be one of the possible reasons that may induce endolymphatic hydrops and lead to Meniere's disease.

Objective: The aim of this study is to prove the involvement of the immune response in the etiopathogenesis of some cochleovestibular disorders by a demonstration of antibodies against inner ear antigens and identify the benefits of immunosuppressive therapy., Background: McCabe in 1979 postulated the hypothesis of autoimmune inner ear disease., Methods: Sodium dodecyl sulfate polyacrylamid gel electrophoresis and immunoblotting were used to examine the serum of 74 subjects for the presence of antibodies against inner ear antigens. The subjects were divided into three groups: A--subjects with idiopathic progressive sensorineural hearing loss, B--subjects with Menière´s disease, C--healthy subjects. Individuals with proven antibodies received immunosuppressive therapy., Results: We detected antibodies against inner ear antigens with molecular weight of 30, 50, 60, 80, 100 kDa. In group A they were found in 52% of 25 subjects, in group B in 44% of 25 subjects and they were not detected in group C. An improvement of hearing was recorded in 69% of subjects in group A. An improvement of hearing was observed in 72%, significant relief of vertigo in 81% of subjects in group B., Conclusion: The present study supports the hypothesis of immune-mediated cochleovestibular disease (Tab. 3, Ref. 15).

Conclusion: Twenty-five rats were challenged by an immunologic attack of the endolymphatic sac. After 6 months, distortion product oto-acoustic emissions (DPOAE) revealed a dysfunction of the outer hair cells and immunological active cells were observed in the endolymphatic sac. This information could contribute to the understanding of Ménière's disease., Objectives: This study investigated if an autoimmune challenge of the endolymphatic sac could affect DPOAE output measurements in rats. Also, a potential autoimmune cell infiltration of the endolymphatic sac was investigated., Methods: Eighteen Lewis rats were immunized with a crude endolymphatic sac extract in complete Freund's adjuvant. Seven control animals were injected with Freund's adjuvant in saline. Cochlear damage was estimated by DPOAE dynamics 3 weeks and 6 months after the immunization. Infiltrative cells in the endolymphatic sac were investigated with transmission electron microscopy., Results: The hearing assessment 6 months after immunization revealed a reduction of the DPOAE, on the full range of frequencies (2-63 kHz) in an average of the mean, of 2 dB ± 1.1 in the immunized group compared to the controls (p < 0.05). The same test showed a 2.5 dB decrease from 2 to 5 kHz (p < 0.01). Immunological active cells were observed in the endolymphatic sac in most of the immunized rats.

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.

Purpose of Review: To examine evidence supporting the association of allergy and Menière's disease., Recent Findings: Animal studies have shown evidence that a provoked systemic immune challenge can result in an allergic reaction within the inner ear, whereas premedication with leukotriene antagonists can prevent the development of endolymphatic hydrops. In human subjects, further data support a heightened allergic response in patients with Menière's disease, whereas pharmacological treatments that target histamine receptors help to control vertiginous symptoms. However, the relationship of migraine with a history of allergy and Menière's disease may confound this association., Summary: Although the evidence of a causal association between allergy and Menière's disease is inconclusive, the inclusion of allergy control as part of the treatment plan for Menière's disease is low risk to the patient and should be considered for patients with indications that include history of seasonal or food allergy, childhood or family history of allergy, bilateral Menière's symptoms, or a development of symptoms within a short time after exposure of food or inhaled allergen.

PURPOSE This study compared clinical features, predisposing factors, and concomitant diseases between sporadic and familial Ménière's disease (MD). METHOD Retrospective chart review and postal questionnaire were used. Participants were 250 definite patients with MD (sporadic, n =149; familial, n = 101) who fulfilled the American Academy of Otorhinolaryngology-Head and Neck Surgery (1995) criteria. RESULTS On average, familial patients were affected 5.6 years earlier than sporadic patients, and they suffered from significantly longer spells of vertigo (p = .007). The prevalence of rheumatoid arthritis (p = .002) and other autoimmune diseases (p = .046) was higher among the familial patients, who also had more migraine (p = .036) and hearing impairment (p = .002) in their families. CONCLUSION The clinical features of familial and sporadic MD are very similar in general, but some differences do exist. Familial MD patients are affected earlier and suffer from longer spells of vertigo.

Injury to the endolymphatic sac may play an important role in the pathogenesis of Ménière's disease, an inner ear disorder characterized by hearing loss, tinnitus and attacks of vertigo. Isoimmunization of 16 inbred Lewis rats with a crude endolymphatic sac extract and complete Freund's adjuvant induced hyperactivity of the endolymphatic sac. One group of rats was immunized by a single dose whereas a second group was immunized twice. Control animals were injected with Freund's adjuvant in saline only. Serum was collected from all rats by the end of the study and harvested autoantibodies were tested by immunohistochemistry. The endolymphatic sacs were investigated by transmission electron microscopy. Endolymphatic sac stimulation was observed in all immunized rats. Based on detailed ultrastructural observations, the degree of reactivity seemed proportional to the number of injections and the extent of immunization. Moreover, the ribosome-rich cells seemed hyperactive with an extravagant content of intracellular components: numerous rough endoplasmic reticulum and free ribosomes, morphological signs of extensive endo- and exocytosis, vesicles of material with a density similar to the homogeneous substance of which many were observed to fuse with primary lysozymes. Basolateral foldings were numerous and in the subepithelial capillaries formation of multiple and apposing fenestrations were observed. No endolymphatic sac stimulation was observed in the control animals. Specific ribosome-rich cell alterations identical to those present in the endolymphatic sac of Ménière's disease were observed 21 days after the first immunization. The observations suggest that either an autoantigen or a trophic factor, capable of inducing a hyperactivity of the ribosome-rich cells and an imbalance of the homogeneous substance metabolism, exists in the endolymphatic sac of the rat., (Copyright © 2013 S. Karger AG, Basel.)

Objectives: To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy., Systematic Review Methodology: Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed., Results and Conclusions: Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: Wheat is one of the most common food allergens found in patients with Meniere's disease (MD). Gluten from wheat has been identified to have a etiopathogenetic role in celiac disease, IgE hypersensitivity to wheat disease, and recently to gluten sensitivity. The aim of this study was to verify the incidence of gliadin prick test response in patients affected by MD., Study Design: Prospective individual case-control study., Methods: There were 58 adult patients with definite MD, 25 healthy volunteers, and 25 patients with grass pollen rhinoconjunctivitis tested with skin prick test to gliadin., Results: A total of 33 MD patients (56.9%) proved to be sensitive to gliadin, eight of whom were positive to prick test after 20 minutes, 13 after 6 hours, 11 after 12 hours, and one after 24 hours., Conclusions: This is the first report of gliadin skin test response in MD. Further studies are needed to define the relationship between immune response to wheat proteins and MD symptoms., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: We tested the claim that a significant proportion of patients with Meniere's disease have antibodies to heat shock protein 70 (HSP70) antigen, which may lead to defective endolymphatic sac function and vertigo attacks., Methods: Serum samples were taken from 80 subjects with a "certain" diagnosis of Meniere's disease (American Academy criteria plus electrocochleographic confirmation of endolymphatic hydrops with tone burst stimuli) and were tested for HSP70 antibodies with the OTOblot (hsp70) Western blot assay. The response was recorded as negative, positive, or equivocal. Samples from 80 sex- and age-matched blood donors were used as controls., Results: Of 80 patients with "clinically certain" Meniere's disease, 14 were positive for HSP70 antibodies or equivocal; of 80 controls, 10 were positive or equivocal. There was no significant difference (p=0.239). There was no correlation with bilateral disease, "activity" of Meniere's disease, or stage of Meniere's disease., Conclusions: Patients with an unequivocal diagnosis of Meniere's disease do not have a significantly raised incidence of HSP70 antibodies.

Ménière's disease (MD), which by definition is idiopathic, has been ascribed to various causes, including both inhalant and food allergies. Patients with MD report higher rates of allergy history and positive skin or in vitro tests compared with a control group of patients with other otologic diseases and to the general public. Recent immunologic studies have shown higher rates of circulating immune complexes, CD4, and other immunologic components in patients with MD compared with healthy controls. Published treatment results have shown benefit from immunotherapy and/or dietary restriction for symptoms of MD in those patients who present with both allergy and MD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Both genetic and environmental factors seem to play role in the etiology of Meniere's disease (MD). Several genes may be involved in susceptibility of MD including Human Leukocyte Antigens (HLA). The associations between MD and HLA alleles have been previously studied in other populations and certain HLA alleles were shown to be predisposing. The aim of this study was to determine the association between HLA-C allele frequencies and definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center in Tehran. Patients with definite MD (N=22) enrolled according to the diagnostic criteria of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Cases with all 3 symptoms of MD (Vertigo, Tinnitus and lower frequency of sensory-neural hearing loss) were included and those with suspected MD were excluded from study. HLA-Cw allele frequencies were determined in patients non-related healthy controls (N=91) using PCR -SSP. We found that the frequency of HLACw*04 was significantly higher in patients compared to the controls [P = 0.0015, OR; 20, 95% CI (3.7-196.9)]. Our results revealed that HLA-C is a genetic predisposing factor in definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center.

Objectives: To establish the frequency of auto-antibodies anti-HSP 70 using ELISA and Western Blot (WB) methods and to compare the results of each method among patients with the Ménière's Disease (MD) and internal ear diseases (IED) who do not fulfill criteria for MD. Sensibility, specificity and predictive values of anti-HSP70 test in diagnosis of MD were calculated., Study: Prospective, case-control., Methods: Blood samples were collected from 31 patients with MD and 78 patients with non Ménière IED. Data regarding cochlear and vestibular symptoms were obtained and blood sample was tested., Results: ELISA tests results were positive in 4(13%) patients and results of WB were positive in 8(26%) patients. Among patients with positive ELISA results, 1 patient presented active disease and in the remaining 3 patients the disease was inactive. Among the 8 WB positive patients, only 2 patients presented active disease. Statistical analyses did not establish any association between serologic findings and clinical factors of MD., Conclusion: The presence of anti-HSP70 using the ELISA and the WB methods did not demonstrate clinical value for the diagnosis of MD. We did not find association between idiopathic MD nor unspecific etiology MD and the presence of anti-HSP70 auto-antibodies.

Background: Ménière's syndrome appears to be the final common pathway of the mechanisms the inner ear responds to almost any injury. Although the autoimmune disease seems to play a major role, exposure to intense noise can also be a trigger in the appearance and/or aggravation of the disease., Material and Methods: The case of 41 years old musician with a history of ankylosing spondylitis, diagnosed with Ménière's syndrome 5 years ago, is presented. Recently the symptoms became more polymorphic, revealing the association between benign paroxysmal positional vertigo (BPPV), Ménière's syndrome and high frequency hearing loss in an autoimmune background. Besides general, neurological and ENT examination, the diagnostic workup comprised of tonal audiogram, brain stem auditory evoked potentials, computerized dynamic posturography and videonistagmography., Results: The final diagnosis was acute noise trauma, Ménière's syndrome, left horizontal semicircular canal BPPV, bilateral sensorineural sudden aggravated hearing loss in high frequencies (above 9 kHz) and allegedly autoimmune inner ear disease. Treatment with an association of corticosteroids, vasodilators and vitamins combined with Vannucchi's maneuver were followed by a significant relief of the symptoms., Conclusion: Although no causal relationship was found between acoustic trauma and increased endolymphatic pressure, both literature data and the case presented show that intense and prolonged noise exposure may aggravate peripheral vestibular syndrome.

Background: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL)., Methods and Findings: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD., Conclusions: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

Ménière's disease (MD), which by definition is idiopathic, has been ascribed to various causes, including inhalant and food allergies. Patients with MD report higher rates of allergy history and positive skin or in vitro tests compared with a control group of patients with other otologic diseases and to the general public. Recent immunologic studies have shown higher rates of circulating immune complexes, CD4, and other immunologic components in patients with MD compared with normal controls. Published treatment results have shown benefit from immunotherapy and/or dietary restriction for symptoms of MD in patients who present with allergy and MD., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose of Review: Meniere's disease is characterized by episodic vertigo, fluctuating hearing loss, aural fullness and tinnitus. Endolymphatic hydrops, found on post-mortem examination, is the histologic hallmark. Recent research suggests that endolymphatic hydrops results from cytochemical perturbations of unknown etiology that lead to disturbance of the normal endolymphatic fluid homeostasis. This consequent hydropic state or the associated cytochemical perturbations appears to create a neurotoxic environment that ultimately leads to spiral ganglion cell death likely via the apoptotic mechanism. This review highlights some of the recent advances in the understanding of the pathophysiology of endolymphatic hydrops and progressive cochleovestibular deterioration, with emphasis placed on its potential therapeutic implications., Recent Findings: Recent evidence supports that endolymphatic hydrops is possibly an epiphenomenon, and is preceded by perturbation of the normal ionic transport regulatory mechanisms. Furthermore, chronic cochleovestibular deterioration appears to be the result of an excitotoxic response to chronic hydrops. A recently described animal model, the Phex mouse, carrying a mutation in the Phex Hyp-Duk gene, provides a novel insight to genetically regulated postnatal endolymphatic hydrops and a useful tool to expand our understanding., Summary: Despite encouraging recent advances, there are considerable challenges that remain in the development of targeted therapeutic interventions that may offer new avenues of neuroprotection in known cases of Meniere's disease. These advances will hopefully provide pharmacotherapeutic interventions aimed at preventing progressive cochleovestibular dysfunction.

Objective/hypothesis: The aim of this prospective study is to evaluate the possible association between Ménière's disease (MD) and autoantibodies., Methods: Fifty-five patients with definite MD (51 unilateral and 4 bilateral) were matched with 55 patients with unilateral vestibular paresis without cochlear involvement and 55 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, anti-TSH receptor antibody, antithyroperoxidase antibody, antithyroglobulin antibody and of antibodies to non-organ-specific antigens, namely antinuclear antibodies, antibodies to extractable nuclear antigens and antineutrophilic cytoplasmic antibodies., Results: Thirty-three subjects (60%) of the MD group had 1 or more elevated serum autoantibody levels, both organ and non-organ specific; 16 patients (29.1%) with unilateral vestibular paresis had 1 or more elevated serum autoantibody levels, while 13 healthy subjects (23.6%) had 1 or more elevated serum autoantibody levels., Conclusions: Based on our data we speculate that there is a more than a chance association between MD and 'autoimmunity', thus suggesting a hypothetical role of the immune system in MD pathogenesis. In other words, a pathogenetic role of an 'immune dysregulation' in MD patients can be hypothesized.

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a specific diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear system may be affected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and positional vertigo. An autoimmune mechanism seems to be responsible for 6% of unilateral and 16% of bilateral forms of Ménière's disease. Oscillopsia and disequilibrium secondary to a bilateral vestibular paresis are probably caused by an autoimmune response in 5% of cases. Balance disorders of central origin may be due to other immuno-mediated disorders such as multiple sclerosis, brainstem encephalitis and vasculitidis. Aim of this paper is to assess the clinical features of autoimmune vertigo disorders through a systematic literature review.

Objectives/hypothesis: Bilateral Meniere's disease (BMD) is a severe disease that usually results in bilateral severe or profound sensorineural hearing loss and chronic disequilibrium with loss of vestibular function. We examined single nucleotide polymorphisms (SNPs) in the PTPN22 and CTLA4 genes in Caucasian patients with BMD to assess the possible association between these polymorphism and the predisposition and clinical expression of this disease., Study Design: A case control study., Methods: The functional protein tyrosine phosphatase type 22 (PTPN22) SNP (rs2476601, 1858C/T) and CTLA4 SNP (rs231775, 49A/G) were analyzed in 52 patients with BMD and 348 healthy controls by a TaqMan 5' allelic discrimination assay. Data were analyzed by a chi(2) test with Fisher exact test., Results: No association was found between the +49A/G CTLA4 genotype and BMD patients. However, the heterozygote PTPN22 1858C/T genotype was present at a significantly higher frequency in BMD patients than in controls (odds ratio = 2.25, 95% confidence interval: 1.09-4.62; P = .04)., Conclusions: These results suggest that the PTPN22 1858C/T genotype may confer differential susceptibility to BMD in the Spanish population and support an autoimmune etiology for BMD.

Conclusion: Because of the lack of association between a positive test and response to corticosteroid treatment, at present, detection of anti-HSP 70 antibody, tumor necrosis factor (TNF)-alpha, erythrocyte sedimentation rate (ESR), or antinuclear antibody (ANA), does not offer clinically useful information in the treatment of Meniere's disease (MD)., Objectives: The study was designed to investigate the performance of various laboratory tests, including anti-HSP 70, TNF-alpha, ESR, ANA, and anti-phospholipid antibodies, in the diagnosis and treatment response of patients with MD., Patients and Methods: Thirty patients who presented with MD and 30 healthy people were selected as study and control groups, respectively. The laboratory panel included the following tests: anti-HSP 70 antibody immunoassay, TNF-alpha, ESR, ANA, and anti-phospholipid antibodies. The study group was given corticosteroid therapy and separated into two groups: the corticosteroid responders and the corticosteroid non-responders. In the follow-up, repeat audiograms were evaluated to determine the response to treatment., Results: TNF-alpha was found at significantly lower titers in the study group when compared with the control group (p<0.05). Anti-HSP 70 was not found in high titers in the study group. ANA positivity in patients with MD was not statistically different from the control group. There was no significant difference in the treatment response for any of the parameters tested.

Acute or progressive sensorineural hearing loss, with or without vertigo and tinnitus, has a considerable impact upon an individual's quality of life. Sensorineural hearing disorders are more commonly observed in patients with rheumatic disease than in the general population, are more likely to be accompanied by the presence of serum autoantibodies, and might respond to steroid therapy. A subgroup of these disorders seem to be immune mediated, but audiologic presentation and serologic testing do not enable this subgroup to be further defined. Rheumatologists should be prepared to manage patients with known rheumatic disease who develop acute hearing loss and to evaluate referred patients without known rheumatic illness experiencing progressive or refractory sensorineural hearing loss. In this article, we summarize the literature and outline a rational approach for the evaluation and treatment of such patients.

Various aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear-vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66.7% TPO-Ab and 33.3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66.7% TPO-Ab and 33.3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0.0001 versus group A and group B) had significant autoantibody levels (68.4% TPO-Ab; 15.8% TPO-Ab + TR-Ab; 10.5% Tg-Ab; 5.2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.

Ménière's disease (MD), which by definition is idiopathic, has been ascribed to various causes, including both inhalant and food allergies. Patients with MD report higher rates of allergy history and positive skin or in vitro tests compared to a control group of patients with other otologic diseases and to the general public. Recent immunologic studies have shown higher rates of circulating immune complexes, CD4, and other immunologic components in patients with MD compared to normal controls. Published treatment results have shown benefit from immunotherapy and/or dietary restriction for symptoms of MD in patients with both allergy and MD.

This study was conducted to test the hypothesis that antigenic challenge is an important stimulative factor for an episode of endolymphatic hydrops. The study was held in a tertiary care center for patients with probable or definite Meniere's disease. The prick test, which included dietary and inhalant allergens, was applied to all patients with a Multi-Test Applicator (Lincoln Diagnostics, Decatur, Ill). Patients were tested with electrocochleography before and after the prick test. The positive allergen was diluted in 1/10 of a prick test dose, and patients were provoked and tested again. A negative summating potential/action potential (SP/AP) amplitude ratio greater than 0.5 was used as the main outcome measure. Pretest, posttest, and postprovocation SP/AP amplitude ratios were compared. A total of 80 diseased and 16 normal ears of 48 patients with Meniere's disease were assessed. All patients were found to be atopic, but none had allergic symptoms. No symptom like vertigo or fullness was seen after the prick test was performed. In all, 30 patients had tinnitus and fullness in the diseased ear, and 6 patients had vertigo after the provocation. The SP/AP ratio was greater than 0.50 in 23 diseased (29%) and 3 normal (19%) ears before the prick test. After the prick test, 62 diseased (78%) and 13 normal (81%) ears had endolymphatic hydrops. These numbers did not change much after the provocation. Results reported here support the role of antigenic stimulation for episodes of Meniere's disease. Endolymphatic hydrops was the atopic reaction that occurred in most study patients.

Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.

Ménière's disease (MD) is an idiopathic inner-ear disorder characterized by fluctuating hearing loss, episodic vertigo, and tinnitus. Though MD's etiology is unknown, growing evidence suggests that autoimmunity may be involved in its development. The aim of this prospective study was to investigate the presence of anti-heat shock protein 70 (anti-HSP70) antibodies during the acute phase of MD and to relate its presence to the antibody pattern. We examined the sera of 13 patients by Western blot immunoassays for reactivity to bovine inner-ear antigen (anti-HSP70) antibodies. The presence of viral antibodies and autoantibodies (herpes simplex, types 1, 2; herpes zoster; cytomegalovirus; Epstein-Barr; IgM; IgG; cardiolipin; thyroglobulin and thyroperoxidase; and antinuclear, antimitochondrial, and anti-smooth-cell antibodies) were also tested. We found reactivity to HSP70 in only 1 of the 13 MD patients (7.7%), and it occurred during herpes zoster reactivation. We found no relationship between the presence of antibodies to HSP70 and immunological or viral testing.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

Conclusions: For the evaluation of a patient with suspected immune-mediated inner ear disease (IMIED), an exhaustive immunologic work-up study is not recommended if financial resources are limited. Analysis of antinuclear antibodies (ANA) and the immunophenotype of peripheral blood lymphocytes (PBL) proved to be the most useful tests in our population to support the clinical diagnosis of IMIED., Objective: Owing to the lack of specific serological markers for the diagnosis of IMIED, an exhaustive immunologic work-up study for patients with suspected IMIED is usually performed. The aim of this study was to estimate the use of resources and the costs involved in the routine laboratory tests used for the diagnosis of IMIED., Material and Methods: This was a comparative study of two groups of patients with a high suspicion of diverse clinical forms of IMIED who were subjected to different serologic test designs. The cost of the classical immunologic work-up study used for the diagnosis of IMIED (n=125) was estimated in comparison with that of a more restricted examination, based on a recently reported high-risk profile, involving the analysis of ANA and PBL (n=57)., Results: The diagnostic efficiency of the two protocols was similar. The cost of a complete immunologic work-up study was 241.77 euros and that of the limited analysis was 53.12 euros.

This study determined the prevalence of migraine and allergy in patients with Ménière's disease (MD) compared with age- and sex-matched controls. We tested the hypothesis that if migraine and MD is linked by allergy, then allergy should be more prevalent in patients with MD and migraine compared with MD patients without migraine. A web-based questionnaire was used to recruit patients with MD (n = 108) while the control group consisted of patients attending the ENT clinic for other problems (n = 100). The prevalence of migraine and allergy was significantly higher in patients with MD compared with age- and sex-matched controls (p > or = 0.005). In addition, the prevalence of allergy was significantly higher in patients who had both MD and migraine (30/42) than MD alone (26/66,p = 0.002). However, there was no link with any specific allergy types. This study suggests that migraine and MD may be linked by an immunological determinant.

Objective: To evaluate the presence of IgG autoantibodies against the P0 antigen in patients affected by sudden hearing loss and Meniere's disease (MD)., Material and Methods: All patients underwent a tonal audiometric evaluation, tympanometry, evaluation of the stapedial reflex threshold with decay time, determination of auditory brainstem responses and a complete vestibular assessment involving evaluation of spontaneous and positional nystagmus (Frenzel glasses), a head thrust test and a caloric test (Fitzgerald-Hallpike technique). Blood samples were drawn from all patients for the immunologic assessment of IgG antibodies against the P0 antigen (30-kDa protein) of guinea pig inner ear extracts using a Western blot assay., Results: Ten patients affected by sudden hearing loss showed specific IgG antibodies against the P0 protein. Specifically, the P0 positive band was detectable in 5/45 patients with unilateral auditory impairment and in 5/5 of those with bilateral forms of auditory impairment. Among MD patients, the P0 positive band was detectable only in those with bilateral audiovestibular impairment (n = 10). Interestingly, in none of the 35 patients affected by monolateral MD were specific IgG antibodies against the P0 protein detectable., Conclusion: The positive reactions to P0 in all bilateral MD and bilateral sudden hearing loss patients found in this study strongly indicate that these pathologies are the result of an ongoing autoimmune process directed against specific antigens of the inner ear.

Purpose of Review: The role of the immune system in mediating inner ear pathology has received considerable attention over the past two decades. The purpose of this paper is to summarize recent basic science research into the pathogenesis of autoimmune inner ear disease (AIED), review the current diagnostic work-up for patients with suspected AIED, and delineate treatment strategies., Recent Findings: Basic science and clinical studies have been performed to delineate the mechanisms by which autoimmune processes may affect the ear and to develop treatment strategies to reverse this pathology. AIED refers to a rapidly progressive (over a course of weeks to months) sensorineural hearing loss that responds to the administration of corticosteroids. In addition, systemic autoimmune diseases (eg, vasculitides, lupus, Wegener granulomatosis) can secondarily affect the inner ear. Although a number of diagnostic tests for AIED have been advocated, the diagnosis of this entity is still predicated on a positive therapeutic response to corticosteroid administration. Alternate immunosuppressive regimens, designed to be used in patients who cannot be weaned off corticosteroids or whose disease becomes refractory to treatment, have proven to be difficult to develop. Methotrexate, which initially showed promise, has recently been shown to be ineffective in preventing progression of hearing loss. Further research is required to better delineate the pathophysiologic mechanisms involved in AIED and to establish more effective and better tolerated treatment regimens., Summary: The original enthusiasm that was generated by the concept that immune-mediated mechanisms may mediate reversible forms of inner ear pathology has been tempered by the realities conveyed by scientific research. The pathophysiology of AIED is still not well understood. Multiple potential mechanisms have been identified that can result in immune-mediated inner ear pathology. The diagnosis of AIED is based on clinical presentation and response to the administration of corticosteroids. Diagnostic testing may support the diagnosis, and the results of a recent multicenter study should clarify the role of immunologic testing in the diagnosis of this entity. Treatment options are limited, with corticosteroids being the only validated treatment option, and methotrexate offering no significant benefit to patients. The role of cyclophosphamide is restricted to patients willing to endure the attendant risks. With the advent of cochlear implants, the administration of toxic medications to preserve hearing at all costs is a less desirable option.

The aim of this article is to evaluate the role of allergy in the pathogenesis of Meniere's disease by means of cytokine profiles, allergic parameters and lymphocyte subgroups. A total of 46 patients aged between 26-68 years diagnosed with Meniere's disease between 1993-2002 were recruited to this study. The control group consisted of 46 healthy volunteers who were from the same age group, living in the same region and possessing similar socioeconomic indicators. Lymphocyte subgroups were measured from the peripheral blood by employing Becton Dickinson (BD) monoclonal CD4, CD8, CD23 antibodies. IFN-gamma, IL4, total IgE levels, and specific IgE levels pertaining to tree, fungus, fruit, egg-white, cow's milk, wheat flour, corn flour, beef, and rice allergens, in all seasons, were measured and compared in the patient and control groups. In patient serum samples there were positive correlations between CD23 and IgE, CD8 and IgE, CD4/CD8 and IgE, and CD23 and CD8 (p <0.01). There were negative correlations between IL-4 and IFN-gamma, IFN-gamma and IgE, and a positive correlation between IL-4 and IgE. Total IgE levels were above the normal values in 19/46 (41.3 per cent) of the patient group, but the ratio was nine out of 46 (19.5 per cent) in the control group. A history of allergy was found in 31/46 (67.3 per cent) when the patients were questioned. The ratio of a history of allergy was 16/46 (34.7 per cent) in the control group. When specific IgE levels were evaluated the ratio of patients with all the panels negative was eight out of 46 (17.9 per cent), but it was 31/46 (67.3 per cent) in the control group. This study found that the prevalence of allergy was higher in patients with Meniere's disease than in the control group. Thus the authors suggest that allergy should be taken into account when patients with this disease are treated.

Meniere's disease (MD) is an idiopathic inner ear disorder characterized by fluctuating hearing loss, episodic vertigo and tinnitus. Its aetiology is unknown, although there is growing evidence that autoimmunity may be involved in its development. Using the Western blot immunoassay, we examined the reactivity to bovine inner ear antigens of sera from a series of MD patients who had previously been extensively studied for the presence of antibodies to collagens and membrane proteins. Reactivity to inner ear antigens of molecular weight 44 and 53 kD was found in 11/25 (44%) and 10/25 (40%) of the patients, respectively; both antigens were absent in the sera of healthy donors. It is still unclear whether the antibodies to 44 and 53 kD proteins play a role in the pathogenesis of MD or if they instead represent the result of inflammation and tissue destruction. Even if the latter is true, they may contribute to the perpetuation of the disease or play a role as a cofactor in association with other mechanisms.