Autoimmune Sensorineural Hearing Loss Research Articles

Autoimmune hearing loss and a chance of its development in children: literature review and own observations

Autoimmune sensorineural hearing loss (AiSNHL) is an uncommon auditory disorder characterized by rapidly progressive bilateral hearing loss and a positive clinical response to treatment with corticosteroids and cytostatics. The prevalence of the disease in the adult population is less than 1% among all cases of subacute and permanent sensorineural hearing loss (precise data are unknown), it is even rarer in children. AiSNHL can be primary (isolated, organ-specific) or secondary (manifestation of another systemic autoimmune disease). The pathogenesis of AiSNHL is based on the proliferation of autoaggressive T cells and the pathological production of autoantibodies to the protein structures of the inner ear, which leads to damage to various parts of the cochlea (possibly also to the retrocochlear parts of the auditory system), less frequently to the vestibular labyrinth. Pathologically, the disease is most often represented by cochlear vasculitis with degeneration of the vascular stria, damage to hair cells and spiral ganglion cells, and endolymphatic hydrops. In 50% of cases, the result of autoimmune inflammation may be fibrosis and/or ossification of the cochlea. The most characteristic symptoms of AiSNHL at any age are episodes of sudden progression of hearing loss, fluctuations of hearing thresholds, and bilateral, often asymmetric impairments. The article presents contemporary ideas of the clinical and audiological manifestations of AiSNHL, the possibilities of diagnosing and treating the disease, and highlights the current approaches to (re)habilitation. Along with literature data, two own clinical cases of an extremely rare pediatric AiSNHL are given.

The use of gene-modified bone marrow mesenchymal stem cells for cochlear cell therapy

BackgroundThe aim of this study was to investigate the potential of using bone marrow mesenchymal stem cells (BMSCs) for treatment of inflammation and autoimmune sensorineural hearing loss. MethodsFifty-five immunized guinea pigs were divided into five groups. Group A received BMSCs expressing IL-4, group B received BMSCs expressing an empty carrier vector, group C received recombinant lentivirus expressing IL-4, group D received recombinant lentivirus expressing an empty carrier vector, and group E received phosphate-buffered saline. Auditory function was monitored using brain stem responses (ABRs) to evaluate the auditory changes. The distribution of implanted BMSCs in the inner ear was estimated using fluorescence microscopy. The distribution and expression of IL-4 gene products in the inner ear were detected via immunohistochemistry. ResultsAfter transplantation, the ABR III wave threshold decreased significantly in BMSCs expressing exogenous IL-4 group (group A), BMSCs expressing empty carrier vector group (group B), and recombinant lentivirus expressing IL-4 group (group C) (P < 0.001), which means the auditory functions of the experimental guinea pigs were improved. Further statistical analysis revealed that BMSCs expressing exogenous IL-4 group (group A) and BMSCs expressing empty carrier vector group (group B) were able to improve the auditory function more obviously (P < 0.05). Lentivirus-infected BMSCs were able to migrate to the inner ear. Fluorescence-positive BMSCs were scattered in the scala tympani and vestibule. ConclusionsThese results demonstrated that BMSCs expressing exogenous IL-4 successfully migrated into the inner ear in an in vitro study. BMSCs expressing exogenous IL-4 and BMSCs can be used to treat inflammatory injury in autoimmune inner ear diseases.

Long-term (16–26 years) follow-up outcome of steroid therapy in refractory autoimmune sensorineural hearing loss

Autoimmune sensorineural hearing loss (ASHL) is a rare disease of uncertain etiology, with no established treatment strategy. The duration of morbidity is increased in refractory cases; and therefore, the preservation of hearing and the prevention of adverse effects with steroid therapy are serious long term issues to consider. Long-term follow up of patients treated for ASHL was performed retrospectively in order to elucidate the pathogenesis of ASHL, evaluate the consequences of steroid therapy, and determine a promising treatment course. The cohort in this study consists of four female patients with refractory ASHL that were followed for 16–26 years. Three patients already had profound deafness on one side, probably due to ASHL, before the initiation of steroid treatment. ASHL was managed with steroid administration and the hearing was evaluated through regular audiometric tests (173–212 times). The relationship between pure tone threshold average and steroid dose was reviewed over a long-term follow-up period for each patient. During follow-up, hearing deficit progressed rapidly several times in all patients, as did responsiveness to steroid therapy. Long-term high-dose steroid therapy was not required for hearing maintenance. Hearing thresholds were nearly maintained in three patients during the 16- to 21- year follow-up, and gradually declined over a 26-year follow-up period in one patient. Considering the progress due to presbycusis, the maintenance of hearing was considered sufficient in all patients. No serious adverse effects were observed in any of the patients. Management of patients affected by ASHL with regular audiometry allowed for hearing maintenance without the morbidity of prolonged steroid therapy. The current observations give insight into the pathogenesis of ASHL pathogenesis and establish an efficient course of treatment.

Immune-mediated sensorineural hearing loss: prevalence and treatment strategies

Autoimmune sensorineural hearing loss is a rare clinical entity which accounting for less than 1% in all cases with hearing loss. The prevalence of hearing loss in immune-mediated inner ear diseases, as shown in case reports or single-center statistics, varies widely. We reviewed the current literatures on the association between sensorineural hearing loss and autoimmune diseases, focused on the prevalence of hearing loss in different autoimmune diseases, treatments and challenges.

Does celiac disease cause autoimmune sensorineural hearing loss?

The primary aim of this study is to identify whether an autoimmune sensorineural hearing loss is an extraintestinal neurological manifestation in adult CD patients. The secondary aim is to identify whether the duration of a gluten-free diet has an effect on the hearing levels of CD patients. This prospective study consisting of 103 adult CD patients and 79 healthy controls between May 2012 and August 2018 at the University of Gaziantep Gastroenterology and Otorhinolaryngology Departments. CD patients were divided into two groups as remission or active, according to their gluten-free diet duration and serum levels of anti-t-TG. The control group was checked both for CD symptoms and anti-t-TG serum levels. Both participants performed a pure tone audiometry after detailed ear nose and throat examination. Only 4 of 103 CD patients showed sensorineural hearing loss. There was no statistically significant difference between hearing levels of the CD patients and the control group in both measurements of air and bone conductions. The hearing levels comparing the remission and active CD patients did not show any difference in air and bone conduction frequencies. In this study with a higher number of CD patients when compared with the previous studies, it has been shown that CD does not appear to cause autoimmune sensorineural hearing loss. In addition, the status of the patients regarding the activeness or the remission of CD did not display a differ between the CD patients in terms of hearing levels.

A Case of Pembrolizumab Induced Autoimmune Sensorineural Hearing Loss

increasingly used to treat a variety of cancers by enhancing the immune response against cancer cells. Pembrolizumab is a humanized antibody which prevents tumor cells from deactivating host T-cells. Like most forms of immunotherapy, many of the adverse effects are autoimmune in origin due to the heightened immune response. Case: We present a rare case of Pembrolizumab induced autoimmune hearing loss in a patient with invasive melanoma which was responsive to steroids. A 67-year-old male presented with metastatic melanoma of the toe. He underwent amputation followed by treatment with IV pembrolizumab 2 mg/kg every 3 weeks. After a single dose, he experienced severe bilateral sensorineural hearing loss. His treatments were stopped and he was started on oral steroids. He later also underwent intratympanic steroid injection. He ultimately achieved improvement to normal-to-mild hearing loss levels in conversational frequencies with subjective return to baseline hearing. According to the FDA, this is one of 14 reported cases of autoimmune hearing loss from Pembrolizumab. Conclusion: Autoimmune hearing loss is a rare, but significant adverse effect of Pembrolizumab treatment for advanced melanoma which is responsive to steroids started up to 4 weeks after onset. While heightened awareness of this response is necessary, we do not recommend routine audiograms in patients undergoing treatment.

Prevention of Hearing Loss by Alteration of the Systemic Immune System

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4+ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

Retracted: Exogenous IL-4-Expressing Bone Marrow Mesenchymal Stem Cells for the Treatment of Autoimmune Sensorineural Hearing Loss in a Guinea Pig Model.

[This retracts the article DOI: 10.1155/2014/856019.].

Choroidal Thickness and En Face Optical Coherence Tomography Imaging in Autoimmune Retinopathy

A 57-year-old white woman developed autoimmune retinopathy (AIR) in both eyes associated with bilateral autoimmune sensorineural hearing loss. Laboratory testing was positive for 68kDa (heat-shock protein) and 136kDa (human interstitial retinoid-binding protein). Extensive cancer screening was negative. Spectral-domain optical coherence tomography enhanced depth imaging demonstrated a markedly thickened choroid in both eyes. En face imaging showed a distinctive pattern of granular hyperreflective foveal dots. The concurrent sensorineural hearing loss was thought to be of autoimmune origin and also responded to immunosuppressive treatment. Eyes with non-paraneoplastic, seropositive AIR may have associated increased choroidal thickness. Audiology testing should be considered.

The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss

The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4+CD25+Foxp3+T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.This article is part of a Special Issue entitled <IEB Kyoto>.

Serum immunoglobulins in 28 adults with autoimmune sensorineural hearing loss: increased prevalence of subnormal immunoglobulin G1 and immunoglobulin G3.

BackgroundOur informal observations suggested that some patients with acute sensorineural hearing loss (ASNHL) have subnormal serum immunoglobulin (Ig) levels. We evaluated 28 consecutive adults (18 men, 10 women) at ASNHL diagnosis using: antibodies to 68 kD protein, 30 kD protein, and type II collagen; and serum total IgG, IgG subclasses, total IgA, and IgM. Reference ranges for Ig levels were mean ± 2 SD. We compared prevalences of subnormal IgG subclasses to those in 275 healthy European adults in previous reports. We also reviewed charts of consecutive adult index patients with primary Ig deficiency (35 common variable immunodeficiency, 406 IgG subclass deficiency) to identify other patients with probable ASHNL.ResultsMean age was 53 ± 10 (SD) y. Six patients (21.4%) had other autoimmunity manifestations. Antibodies to 68 kD protein, 30 kD protein, and type II collagen were detected in 21.4% (6/28), 21.1% (4/19) and 18.8% (3/16), respectively. Three patients (10.7%) had subnormal IgG1, six (21.4%) had subnormal IgG3, and four (14.3%) had subnormal IgG1 and IgG3. Some had subnormal IgG2, IgG4, IgA, and IgM (n = 1, 2, 3, and 1, respectively). Prevalences of subnormal IgG1 or IgG3 were greater in ASNHL patients (25.0% and 35.7%) than 275 controls (2.1% and 3.3%), respectively (p < 0.0001, each comparison). Relative risks of subnormal IgG1 and IgG3 in ASNHL were 11.5 [95% CI: 4.1, 31.7] and 10.9 [4.8, 25.6], respectively. Hearing improved after initial therapy in 17 patients (60.7%). Multiple regressions on Ig levels revealed no significant associations with other available variables. Logistic regressions on initial therapy response revealed a positive association with men (p = 0.0392) and a negative association with IgA (p = 0.0274). Our estimated prevalence of probable ASNHL in 35 patients with common variable immunodeficiency during a follow-up interval of 8 ± 4 y was 0% [95% CI: 0, 12.3]). Prevalence of probable ASNHL in 406 patients with IgG subclass deficiency during the same interval was 0.74% [0.19, 2.33].ConclusionsSerum levels of IgG1 or IgG3 were subnormal in 46.4% of 28 patients with ASNHL. Among adults who present with primary Ig deficiency, some may have or later develop ASNHL.

Long-term efficacy of infliximab in autoimmune sensorineural hearing loss associated with rheumatoid arthritis

Long-term efficacy of infliximab in autoimmune sensorineural hearing loss associated with rheumatoid arthritis

Experimental Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss

This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL.

Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a guinea pig model.

Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

Identification of autoantibodies against inner ear antigens in a cohort of children with idiopathic sensorineural hearing loss

Immune-mediated pathogenesis has been suggested for idiopathic sensorineural hearing loss. Recent studies have investigated the relationship between idiopathic sensorineural hearing loss and autoantibodies against inner ear antigens. We conducted a prospective, observational study in a series of pediatric patients affected by idiopathic sensorineural hearing loss. Autoantibodies against inner ear (anti-Cogan peptide, anti-connexin 26, anti-DEP1/CD148 and anti-reovirus), previously described in the serum of patients with Cogan’s syndrome, were detected in our population. The characteristics of children whose results were positive were also evaluated to verify if clinical data, disease progression and response to treatment could confirm an immune-mediated pathogenesis. Eleven patients were enrolled and 9 of them were positive for inner ear antibodies. Non-organ specific autoantibodies were present in 5 children out of 9. An immune-mediated condition was diagnosed in 2 cases and minor immune manifestations were found in 2 additional patients. In 5 cases hearing loss remained stable without therapy, while 4 children developed progression. Two subjects were treated with corticosteroids and methotrexate, achieving hearing improvement. Another subject showed stabilization on methotrexate. Inner ear autoantibodies can be positive in children with autoimmune sensorineural hearing loss, and in conjunction with clinical data may assist the clinician in identifying a subset amenable for immune modulation therapy. Large prospective studies are needed to investigate usefulness, diagnostic and prognostic role of these autoantibodies.

Autoimmune sensorineural hearing loss: the otology-rheumatology interface

Autoimmune sensorineural hearing loss (SNHL) is a rare clinical entity characterized by a progressive fluctuating bilateral asymmetric SNHL that develops over several weeks to months. Vestibular symptoms, tinnitus and aural fullness are present in up to 50% of patients. Due to the lack of specific diagnostic tests, both clinical suspicion and responsiveness to corticosteroids are the pillars for the diagnosis of autoimmune SNHL. The evaluation of patients in whom this condition is suspected should include a detailed history and physical examination, an audiogram, an MRI and a limited laboratory workup to exclude secondary causes of hearing loss. The low frequency of this condition, the heterogeneity in the designs of the available studies and the absence of randomized trials comparing treatment responses and assessing long-term outcomes are some of the factors accounting for the limited evidence to guide the clinician in the approach to the diagnosis and treatment of autoimmune SNHL.

Atypical Meniere Disease: Case Report of a Patient Treated as Sudden Hearing Loss

Meniere's disease is an idiopathic disease involving the inner ear, which is characterized by fluctuating low frequency sensorineural hearing loss, tinnitus, aural fullness, and recurrent vertigo. We could see the Meniere's disease without vestibular symptom in some cases. These cases have been reported as atypical (Cochlear) Meniere's disease. We have evaluated a patient of atypical Meniere's disease followed as sudden hearing loss with fluctuating low tone type sensorineural hearing loss without vertigo. Sudden deafness, cochlear sensorineural hearing loss, chronic progressive sensorineural hearing loss, presenile presbycusis, noise induced and autoimmune sensorineural hearing loss may be confused in diagnosis of Meniere disease. Key words: Atypical Meniere Disease; Hearing Loss; Diagnosis.

Sensorineural Hearing Loss in the Setting of Systemic Autoimmune Disease: A Temporal Bone Study

Objective: Determine if temporal bone specimens from patients with different systemic autoimmune diseases and sensorineural hearing loss will show similar histologic findings, including endolymphatic hydrops, strial atrophy, loss of hair cells, neuronal loss, and/or evidence of vasculitis. Method: This is a histopathologic study of 34 temporal bones from 21 patients with autoimmune disorders and sensorineural hearing loss. Specimens were studied under light microscopy, and pathologic changes were graded, including degree of endolymphatic hydrops, strial atrophy, hair cell loss, neuronal loss, and presence of vasculitis. Results: Strial atrophy was the most common finding and correlated with the degree of hearing loss. Only patients with Cogan syndrome or primary autoimmune sensorineural hearing loss had endolymphatic hydrops. Cochlear hair cell loss and neuronal loss were seen in some specimens but not universally. Vasculitis was only seen in polyarteritis nodosa. Conclusion: Strial atrophy may represent the underlying etiology of sensorineural hearing loss in patients with systemic autoimmune diseases. However, the age of these patients makes presbycusis a possible confounding factor in these specimens.

Treatment-Refractory Autoimmune Sensorineural Hearing Loss: Response to Infliximab

We conducted a retrospective study to assess the effects of infliximab, a chimeric monoclonal antibody, on hearing in patients with autoimmune sensorineural hearing loss who had previously not responded to steroid therapy and/or treatment with other immunosuppressive drugs such as methotrexate and cyclophosphamide. We reviewed the records of 8 such patients. Our objective measures of outcome were pure-tone averages at 500, 1,000, 2,000, and 3,000 Hz and speech discrimination scores. At the completion of treatment, no patient exhibited a positive response to infliximab therapy by objective measurements, and only 1 patient (12.5%) reported subjective improvement.

Dr. Radic, et al reply

To the Editor: We thank Conway and colleagues for their interest in our article1. The major thrust of our report was not to debate whether biological therapy is good or bad, beneficial or not, for autoimmune sensorineural hearing loss (AISNHL) treatment. Our purpose was to present a very interesting case report of successful use of … Address correspondence to Dr. M. Radic, University Hospital Split, Department of Rheumatology, Soltanska 1, Split 21000, Croatia. E-mail: mislavradic{at}gmail.com