Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease.

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.

Density of Macrophages Immunostained With Anti-iba1 Antibody in the Vestibular Endorgans After Cochlear Implantation in the Human.

HYPOTHESIS: Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human. BACKGROUND: Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation. METHODS: The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared. RESULTS: The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears. CONCLUSION: An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium.

Can a plantar pressure-based tongue-placed electrotactile biofeedback improve postural control under altered vestibular and neck proprioceptive conditions?

We investigated the effects of a plantar pressure-based tongue-placed electrotactile biofeedback on postural control during quiet standing under normal and altered vestibular and neck proprioceptive conditions. To achieve this goal, 14 young healthy adults were asked to stand upright as immobile as possible with their eyes closed in two Neutral and Extended head postures and two conditions of No-biofeedback and Biofeedback. The underlying principle of the biofeedback consisted of providing supplementary information related to foot sole pressure distribution through a wireless embedded tongue-placed tactile output device. Center of foot pressure (CoP) displacements were recorded using a plantar pressure data acquisition system. Results showed that (1) the Extended head posture yielded increased CoP displacements relative to the Neutral head posture in the No-biofeedback condition, with a greater effect along the anteroposterior than mediolateral axis, whereas (2) no significant difference between the two Neutral and Extended head postures was observed in the Biofeedback condition. The present findings suggested that the availability of the plantar pressure-based tongue-placed electrotactile biofeedback allowed the subjects to suppress the destabilizing effect induced by the disruption of vestibular and neck proprioceptive inputs associated with the head extended posture. These results are discussed according to the sensory re-weighting hypothesis, whereby the CNS would dynamically and selectively adjust the relative contributions of sensory inputs (i.e. the sensory weights) to maintain upright stance depending on the sensory contexts and the neuromuscular constraints acting on the subject.

Immune-mediated audiovestibular disorders in the paediatric population: a review.

Recent studies show that several audiovestibular pathologies in the paediatric population may be immune-mediated. This is even more probable if the pathology is associated with a coexisting systemic autoimmune disorder. At this time, however, the current literature is limited to a few case reports, and little is known with regard to prevalence, diagnosis, and management of immune-mediated inner-ear disorders in children. This review aims to shed some light on clinical presentation, diagnosis, and treatment of paediatric immune-mediated inner-ear disorders. Sudden and progressive sensorineural hearing loss is discussed, in addition to some of the systemic autoimmune disorders commonly associated with immune-mediated audiovestibular pathology such as Cogan's syndrome, systemic lupus erythematosus, Behcet's disease, Sjogren's syndrome, and juvenile idiopathic arthritis.

Efferent neurotransmitters in the human cochlea and vestibule.

CONCLUSION: Current neurotransmission models based on animal studies on the mammalian inner ear not always reflect the situation in human. Rodents and primates show significant differences in characteristics of efferent innervation as well as the distribution of neuroactive substances. OBJECTIVE: Immunohistochemistry demonstrates the mammalian efferent system as neurochemically complex and diverse: several neuroactive substances may co-exist within the same efferent terminal. Using light and electron microscopic immunohistochemistry, this study presents a comparative overview of the distribution patterns of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, GABA, CGRP, and enkephalins within the peripheral nerve fiber systems of the human inner ear. MATERIALS AND METHODS: Human temporal bones were obtained post mortem and prepared according to a pre-embedding immunohistochemical technique to detect immunoreactivities to ChAT, GABA, CGRP, leu- and met-enkephalins at the electron microscopic level. RESULTS: Immunoreactivities of all the antigens were present within both the lateral and medial efferent systems of the cochlea, whereas only ChAT, GABA, and CGRP were detected in efferent pathways of the vestibular end organs.

Immunoelectron microscopic analysis of a novel carbohydrate differentiation antigen (CDA-3C2) in the developing rat olfactory and otic systems.

A carbohydrate differentiation antigen (CDA-3C2) exhibits a highly specific and restricted pattern of expression during rat embryogenesis. In the periphery of the embryo, this antigen is associated transiently with the lateral ectoderm but is retained only in the olfactory and otic epithelium throughout morphogenesis. At the light microscopic level, CDA-3C2 immunoreactivity appears mostly along cell periphery and in the extracellular matrix. The aim of the present study was to determine the specific cellular and subcellular distribution of CDA-3C2 in vivo in order to identify potential sites of cellular and tissue function of the antigen during embryogenesis. There was a strikingly similar subcellular distribution of CDA-3C2 in the developing otic and olfactory systems, found mostly along cell membranes, microvillar projections and acellular secretions of the epithelium. Mature sensory components of the epithelia were not immunoreactive, whereas supportive cells and their secreted structures were densely stained. The highly coincident nature of CDA-3C2 in both sensory epithelia suggests that this carbohydrate epitope, and possibly its carrier macromolecule, participate in a morphogenetic function common to these two sensory epithelia.

Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear.

The 275 kD hair cell antigen (HCA) is a protein that is specifically associated with the apical surface of sensory hair cells in the chick inner ear. A comparative study of the vestibular and auditory organs of the inner ear, using both wholemounts and cryosections double labelled for the HCA and F-actin, reveals that two distinct types of hair cells can be distinguished on the basis of antibody staining in each of the vestibular epithelia. One type of hair cell has the HCA restricted to the base of the stereocilia bundle and is found in the striolae of the maculae and in a large, centrally located region of each ampulla. The other type of hair cell is found in the extrastriolar regions of the maculae and the peripheral regions of the ampullae and has the HCA distributed over the entire surface of the stereocilia bundle. In the basilar papilla, the auditory epithelium of the chick inner ear, the HCA is, as in the striolar regions of the maculae, restricted to the base of the hair bundles. In all sensory epithelia the HCA is also present on the apical, nonstereociliary surface of the hair cells. Ultrastructural examination of the basilar papilla and the striolar and the extrastriolar regions of the lagenar macula after staining with ruthenium red and tannic acid shows that there are four morphologically different types of interstereociliary connectors (oblique tip connectors, horizontal tip connectors, shaft connectors and basal connectors) associated with the hair bundles. Oblique tip connectors and basal connectors are found on hair cells from all regions and have a similar distribution. Horizontal tip connectors are seen only on hair cells in the basilar papilla and the striolar region of the lagenar macula. Shaft connectors extend all the way to the tips of extrastriolar hair cell bundles, but extend only a short way up the bundles of hair cells in the basilar papilla and striolar region of the lagenar macula. Immunogold labelling confirms the results obtained with immunofluorescence microscopy and demonstrates that the distribution of the HCA on the surface of adjacent stereocilia correlates closely with that of the shaft connectors; i.e., immunostaining is observed up to the tips of the extrastriolar hair cell bundles, but is restricted to the lower regions of hair cell bundles in the striolar region and basilar papilla.(ABSTRACT TRUNCATED AT 400 WORDS)

Appearance and development of neuron-specific enolase immunoreactivity in organotypic cultures of mouse embryo otocysts.

The appearance of neuron-specific enolase (NSE) immunoreactivity was studied in sensory and vestibular ganglion cells during the development of mouse embryo otocysts grown in vitro from the 13th gestation day. NSE appeared sequentially in the ganglion and sensory cell populations of the inner ear with a pattern that paralleled their successive maturation. Comparison with NSE immunoreactivity profile during in vivo development shows that NSE appears earlier during organotypic in vitro maturation.

Localization of substance P-like immunoreactivity in guinea pig vestibular endorgans and the vestibular ganglion.

The immunocytochemical distribution of substance P (SP) in guinea pig vestibular endorgans and the vestibular ganglion was investigated. Two kinds of SP-immunoreactive fibers were distinguished. Most were thick, and found around or beneath sensory hair cells. These SP-immunoreactive fibers were distributed predominantly on the slope of the crista and the peripheral region of the macula. By electron microscopy, we confirmed this type of SP-like immunoreactivity to be restricted within primary afferent neurons. Some vestibular ganglion cells also showed SP-like immunoreactivity, suggesting that SP is present in some primary afferent neurons, and is involved in afferent neurotransmission. The characteristic distribution of SP may indicate functional differences within each endorgan. The other group of immunoreactive nerve fibers, varicous thin fibers, could be found in the stroma of vestibular endorgans, nerve trunk, vestibular ganglion, and along blood vessels of the vestibular ganglion. These fibers may have a different origin, and have an influence on blood flow and certain other functions.

Inner ear-specific autoantibodies.

The sera of patients with idiopathic sensorineural hearing loss (SNHL) were examined, using qualitative immunoblotting (Western blotting), for the presence of inner ear (IE)-specific autoantibodies. The water-soluble extracts and the sodium dodecyl sulfate-soluble extracts were prepared as the antigens from bovine IE tissues and several other organs in order to determine the specificity of autoantibodies in their sera to the IE. Some patients (n = 46) tested had autoantibodies that reacted with 68-, 62-, 55-, 50-, or 47-kd antigenic determinants found in all tissues, while others (n = 13) showed IE-specific autoantibodies which reacted with 220-, 60-, 58-, 33-35-, or 32-kd determinants. The presence of these autoantibodies from patients with progressive SNHL may have important implications with regard to their etiology and possibly their sensitivity to therapeutic intervention. It is now necessary to purify these IE-specific antigens and determine their clinical usefulness.

Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss.

Recognition of immune-mediated sensorineural deafness that responds to immunosuppressive therapy has led to a search for a diagnostic assay to identify inner ear autoantibodies. Without a confirmed diagnosis of autoimmune disease, many patients have undergone inappropriate immunosuppressive treatment or developed irreversible inner ear damage. Serum from patients with progressive sensorineural hearing loss (n = 54), ulcerative colitis (N = 5), normal controls (N = 14), and animals with experimental autoimmune sensorineural hearing loss (EASNHL) were analyzed by Western blot against fresh bovine inner ear antigen preparations. The hearing loss group (19 [35%]) showed a single-or double-band migrating at 68,000 molecular weight (MW), differing from the normal group (1 of 14 [7%]) which showed a similar band (P = .031). Upon analysis by two-dimensional gel electrophoresis both the EASNHL guinea pigs and a patient reacted against identical components of inner ear antigen. These results suggest an autoimmune basis for disease in patients reacting against the 68,000 MW antigen.

Autoimmune reactivity in Cogan's syndrome: a preliminary report.

Autoimmune inner ear disease was first described by McCabe in 1979. The diagnosis is supported by cell-mediated immune responses to inner ear membrane antigen stimulation. Cogan's syndrome consists of vestibuloauditory dysfunction, ocular inflammation, and nonreactive serologic tests for syphilis. The ocular disease can be controlled by steroids; unfortunately, some patients ultimately become totally deaf. An autoimmune etiology has long been suspected but only recently confirmed by McCabe. In our study two patients with Cogan's syndrome were studied for autoimmune inner ear disease with the use of both cellular and humoral immune tests. Results were compared to normal control subjects. On the basis of test results, preliminary conclusions were that (1) the vestibuloauditory symptoms of Cogan's syndrome are autoimmune in origin; (2) the autoimmune process is mediated through cellular rather than humoral (antibody) pathways; (3) systemic steroids may suppress positive test results; and (4) test results are more likely to be positive when symptoms are acute. Therapeutic implications are significant: the addition of cytotoxic drugs to steroids in selected cases may help prevent total deafness that otherwise might be inevitable.

Immune response of the endolymphatic sac to horseradish peroxidase: immunologic route from the middle ear to the inner ear.

Twenty guinea pigs were immunized with horseradish peroxidase (HRP) intradermally and challenged with 5 mg of the same antigen in the tympanic bulla. The appearance of immunoglobulin-producing cells (plasma cells) in the inner ear structure was examined immunohistochemically in frozen sections. Four to 10 days following antigen challenge, 5 of the 20 animals showed significantly increased plasma cells in the subepithelial connective tissue of the endolymphatic sac (ES). Those cells showed positive reactions, mainly with IgG followed by IgM. The cells that reacted positively with IgA were few. Some of these plasma cells were considered to contain the specific antibody against HRP. The results indicate the role of the ES as a local immune response region for the inner ear complex, as well as the existence of an immunologic route from the middle ear cavity to the inner ear, particularly to the ES.

Immunohistochemical identification and localization of actin and fimbrin in vestibular hair cells in the normal guinea pig and in a strain of the waltzing guinea pig.

Using immunohistochemical methods, actin and fimbrin were identified and localized in vestibular epithelia iin the normal guinea pig and in the waltzing guinea pig. In the normal guinea pig, actin was found in the stereocilia and in the cuticular plate. Fimbrin was detected in the stereocilia but surprisingly not in the cuticular plate. As fimbrin was found in the cuticular plates in cochlear hair cells it is suggested that the hair cells in the two organs have different mechanoreceptor properties which can demand different cuticular plate stability. In the waltzing guinea pig, actin was found in the stereocilia, in the rod and n the cuticular plate. Fimbrin was seen in the stereocilia and in the rod, but could not be detected in the cuticular plate. These results emphasize the resemblance between the rod and the stereocilia. It is suggested that the rod is a genetically induced pathological intracellular type of stereocilium which grows in an uncontrolled manner.

[Effect of inner ear immune response on vestibular function in guinea pigs].

We examined vestibular dysfunction and histological damage caused by direct antigen challenge to the endolymphatic sac in guinea pigs. We observed spontaneous nystagmus every eight hours and performed caloric testing every week following endolymphatic sac secondary KLH challenge. Spontaneous nystagmus was seen in 12 of 18 animals, and nystagmus in all directed toward the unchallenged ear (paralytic). The caloric response time courses were classified into two types, which were irreversible type and reversible type after endolymphatic sac KLH challenge. The immune injury of animals with irreversible type was thought to be stronger than that of these with reversible type. The spontaneous nystagmus of irreversible type animals was longer than that of reversible type animals. The temporary vestibular dysfunction was thought to be similar to that observed in Meniere's disease.

[Inner ear diseases of probable autoimmune origin and its response to steroid treatment]. / Patología de oído interno de probable origen autoinmune y su respuesta al tratamiento esteroideo.

Cellular and/or humoral immune reactions may be involved in the development of some cochleovestibular dysfunctions long considered idiopathic. In a clinical study of 98 patients, 82 of them with cochleovestibular disorder, a battery of immunologic studies was used. Thirty-one patients received steroid treatment, of which 19 obtained good results; 5 of these patients had positive serum antibodies.

[Impairment of microbial environment of the colon in angiogenic cochleo-vestibulopathies and lipid distress syndrome]. / Narushenie mikrobnoi ékologii tolstoi kishki pri agiogennykh kokhleovestibulopatiiakh i lipidnom distress-sindrome.

We studied structural and metabolic microbiocenosis of the colon in angiogenic cochleovestibulopathies and lipid distress-syndrome by gas-liquid chromatography estimation of the level and spectra of volatile fatty acids, secretory immunoglobulin A, coprological test in 47 patients. As a result, disbiotic affection of the intestine in lipid distress-syndrome is characterized, ways of microflora normalization are shown.

Characterization and inflammatory response of perivascular-resident macrophage-like melanocytes in the vestibular system.

A large number of perivascular cells expressing both macrophage and melanocyte characteristics (named perivascular-resident macrophage-like melanocytes, PVM/Ms), previously found in the intra-strial fluid-blood barrier, are also found in the blood-labyrinth barrier area of the vestibular system in normal adult cochlea, including in the three ampullae of the semicircular canals (posterior, superior, and horizontal), utricle, and saccule. The cells were identified as PVM/Ms, positive for the macrophage and melanocyte marker proteins F4/80 and GSTα4. Similar to PVM/Ms present in the stria vascularis, the PVM/Ms in the vestibular system are closely associated with microvessels and structurally intertwined with endothelial cells and pericytes, with a density in normal (unstimulated) utricle of 225 ± 43/mm(2); saccule 191 ± 25/mm(2); horizontal ampullae 212 ± 36/mm(2); anterior ampullae 238 ± 36/mm(2); and posterior ampullae 223 ± 64/mm(2). Injection of bacterial lipopolysaccharide into the middle ear through the tympanic membrane causes the PVM/Ms to activate and arrange in an irregular pattern along capillary walls in all regions within a 48-h period. The inflammatory response significantly increases vascular permeability and leakage. The results underscore the morphological complexity of the blood barrier in the vestibular system, with its surrounding basal lamina, pericytes, as well as second line of defense in PVM/Ms. PVM/Ms may be important to maintain blood barrier integrity and initiating local inflammatory response in the vestibular system.

[Auto-immune sensorineural deafness: physiopathology and therapeutic approach]. / Surdités auto-immunes : bases pathogéniques et applications thérapeutiques.

Sensorineural hearing loss may be due to an autoimmune mechanism. The mechanisms that could induce autoimmune inner ear damage are now better understood, but are not exclusive. Moreover, there is no specific immunologic test available for the diagnosis of autoimmune sensorineural hearing loss, which could also complicate the disease course of other autoimmune systemic diseases. Thus, the incidence of sensorineural autoimmune hearing loss is probably underestimated. The aim of this study was to review the experimental immunologic data in favour of an autoimmune mechanism in this subgroup of sensorineural hearing loss: humoral specific response against inner ear (autoantibodies against a transmembrane transporter) and also cellular response (against cochlin: one of the major proteins expressed in the inner ear). The aim of this review was also to focus on clinical and epidemiological human data that provide evidence for an autoimmune etiopathogeny of some sensorineural hearing loss. Therapeutic options such as immunosuppressive treatments (oral corticosteroids and other immunosuppressive drugs, such as methotrexate and anti-TNFalpha) are also discussed.

GABA immunoreactivity of calyceal nerve endings in the vestibular system of the guinea pig.

Neurotransmitters involved in the vestibular system are largely uncharacterized. On the basis of results of earlier electrophysiological and immunohistochemical experiments, glutamate and gamma-amino-butyric acid (GABA) have been proposed in both mammalian and non-mammalian species as afferent transmitters between the sensory cell and the afferent dendrite. GABA is also suspected to act as an efferent neurotransmitter in the cochlea. We describe in this study the immunocytochemical localization of GABA within the vestibular end organs in the guinea pig. GABA immunoreactivity was found in the calyceal nerve endings surrounding type I hair cells of the vestibular epithelia. The most significant labelings were obtained in the crista ampullaris. Labeling was more difficult to observe in the utricular and saccular macula. These results contribute to the recent proposal that the calyx has a secretory function, and suggest that GABA may have a modulatory influence upon the type I hair cells.