Search

Objectives: Autoimmune inner ear disease (AIED) is a distinct clinical entity from sudden sensorineural hearing loss. The purpose of this study was to investigate the clinical characteristics of AIED in patients with selective IgA deficiency (sIgAD)., Materials and Methods: This retrospective observational study was based on data from the Leumit Healthcare Services database in Israel. We searched all subjects aged ≥12 years who had undergone serum total IgA measurements during 2004-2014 for any reason. The sIgAD patients included all subjects with serum IgA of ≤7 mg/dL (0.07 g/L). A control group was randomly sampled from the full study population (n ≈ 730,000) with a case-control ratio of 10 controls for each case (1:10)., Results: Among 347 subjects with sIgAD, we identified 9 patients with concomitant AIED (sIgAD + AIED group). This group was characterized by a higher prevalence of allergic diseases (8 patients; 88.9%) than sIgAD patients without AEID (sIgAD + AIED group; 153 patients; 45.2%; p = 0.014). Both systemic diseases (3 patients; 33.3%) and organ-specific autoimmune diseases (7 patients; 77.8%) were more prevalent in the sIgAD + AIED group (sIgAD + AIED group: 19 patients 5.5%, p = 0.015; sIgAD - AEID group: 76 patients, 21.9%, p < 0.001), with an OR of 8.39 (1.94-36.19; p = 0.004). sIgAD patients with and without AIED were characterized by a higher prevalence of documented episodes of acute otitis media, allergic diseases, and autoimmune diseases than the control group., Conclusion: The study exposes a significant association between AIED and sIgAD. We believe that sIgAD has to be excluded in AIED patients., (© 2020 S. Karger AG, Basel.)

The triad of central nervous system symptoms, visual disturbance and hearing impairment is an oft-encountered clinical scenario. A number of immune-mediated diseases should be considered among the differential diagnoses including: Susac syndrome, Cogan syndrome or Vogt-Koyanagi-Harada disease; demyelinating conditions such as multiple sclerosis or neuromyelitis optica spectrum disorder; systemic diseases such as systemic lupus erythematosus, Sjögren syndrome or Behcet disease and granulomatous diseases such as sarcoidosis. In this article, we coin the term 'BEE syndromes' to draw attention to the various immune-mediated diseases that affect the brain, eye and ear. We present common disease manifestations and identify key clinical and investigation features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Hypothesis: There are some known reasons for chronic dilatory Eustachian tube dysfunction (chronic D-ETD, also known as chronic obstructive tube dysfunction), for example infections, hyperplastic adenoids, or tumors. In many cases though, none of these reasons apply. The question arises whether there might be an autoimmune pathogenesis in patients with idiopathic chronic D-ETD., Methods: The study includes 31 consecutive patients with chronic D-ETD and 92 consecutive blood donors (BD, comparative cohort). The production of antinuclear antibodies (ANA), as an indicator for autoimmune pathologies, was measured in the serum of patients and BD., Results: ANA titers were significantly higher in patients with chronic D-ETD, compared with BD (p = 0.0027). The results weighted clearly toward higher ANA titers in younger patients. A comparison of ANA titers in patients and BD aged less than 40 years showed a significant difference (p = 0.0062), whereas it was not significant between patients and BD aged ≥ 40 years (p = 0.19)., Conclusion: The significant results of elevated ANA titers in chronic D-ETD make an autoimmune pathogenesis highly probable, at least in some of the patients concerned. Further research with higher numbers of patients is needed to confirm the hypothesis of an autoimmune chronic D-ETD. A better understanding of etiology and pathogenesis of chronic D-ETD might open up new and perhaps even causal therapeutic strategies.

Ear, nose and throat (ENT) manifestations in granulomatosis with polyangiitis (GPA) represent the most frequent symptoms at disease onset. The aim of the study was to analyse ENT involvement at diagnosis, as well as how it could influence relapse rate, mortality and disease severity. A retrospective non-controlled cohort study was performed including all consecutive diagnosed GPA from 1996 to 2016 in two rheumatology centres of Northern Italy, focusing particularly on ENT presenting signs and symptoms at baseline. Eighty-nine patients (48.3% females) with new onset GPA were evaluated. They were mostly Caucasian (97.7%), middle aged (mean 54.5 years) and more frequently anti-neutrophil cytoplasmic antibodies (ANCA) positive (78.6%) with PR3 specificity (81.4%). At diagnosis, ENT involvement was reported in 71.9% patients, second only to systemic symptoms. These patients were significantly younger at disease onset (0.013), with less frequent renal involvement (0.014) irrespectively to ANCA status, but with significantly higher Vasculitis Damage Index (VDI) (0.001). The most frequent ENT manifestation was sinonasal involvement (58.4%, 73% of which with nasal inflammation/chronic sinusitis and 48% with nasal crusting), while otologic involvement (mainly otitis media/otomastoiditis) was observed in 34.8%. ENT-GPA patients presented a higher survival rate at 5 years (98.1 vs 77.7%, 0.049), and ENT involvement resulted to be an independent predictor of better outcome (OR 0.37, 95% CI 0.2-0.8, 0.019). Our data confirms that ENT involvement is not only one of the key clinical features of GPA, but also could point out a milder GPA subset with lower renal involvement and lower mortality rate, irrespectively to ANCA status.

In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation., (© 2017 S. Karger AG, Basel.)

Background: Recently, there have been numerous case reports and series describing patients presenting with cutaneous vasculopathy that has been linked to the levamisole frequently found in cocaine., Objective: The purpose of this study was to review all published case reports and series of patients reported with cutaneous vasculopathic findings of lemavisole induced vasculopathy (LIV) associated with cocaine use., Methods: A review of PubMed was performed searching the keywords: levamisole, cocaine, in combination with vasculitis, and vasculopathy. Twenty-two case reports and series were available with sufficient data on reported patients to be included. Four patients from the authors' clinical experience are included as well., Results: A number of common clinical and pathological findings are reviewed, including lower extremity (46/55 patients, 84%) and ear involvement (40/55 patients, 73%), and positive anti-neutrophil cytoplasmic antibodies (ANCA) findings (p-ANCA 42/48 patients, 88%; anti human neutrophil elastase 11/11 patients, 100%). Similar numbers of patients were treated with systemic corticosteroids as were treated conservatively; there was comparable improvement on follow up., Conclusions: There are a number of clinical and laboratory findings that are commonly found in patients with LIV. There is currently insufficient data to recommend treatment with systemic corticosteroids in patients with this condition.

Background: Information concerning cross-reactivity among metal allergens is scarce. We previously devised a murine metal allergy model using lipopolysaccharide (LPS) as an adjuvant. LPS reduces the minimum allergy-inducing concentration (MAIC) of metals at both the sensitization and the elicitation steps., Objectives: Here, we examined allergic cross-reactivity among some metals in this murine model, and compared the effects of ultrapure (99·99% or more) and low purity (93-99%) metal salts., Methods: A mixture of a metal salt and Escherichia coli LPS was injected intraperitoneally into BALB/c mice (0·25 mL per mouse). Ten days later, metal salts (with or without LPS) were challenged to ear pinnas (20 μL per ear), and ear swelling was measured., Results: Among the ultrapure metals tested (Ni, Pd, Co, Cr, Cu and Au), only Ni and Pd cross-reacted. In this cross-reaction, their MAICs were at the same level. Combined challenge with Ni and Pd at sub-MAICs (but not at higher concentrations) produced an additive effect. Surprisingly, mice sensitized with low purity Ni reacted to all the tested low purity metals (Ni, Pd, Co and Cr), and the low purity metals were shown to contain contaminant metals., Conclusions: In our model: (i) Ni and Pd (members of the same group in the periodic table of elements) cross-react with each other, (ii) this cross-reaction may depend on true and false antigens forming metal-protein complexes with similar spatial geometries, (iii) Co, Cr, Cu and Au do not cross-react with each other, (iv) in low purity materials, trace contaminant metals may be sufficient to evoke allergy, and thus (v) high purity metal salts should be considered for use in clinical patch testing., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

The role of inapparent carriers of Mycoplasma agalactiae and the strategies used to colonise the external ear canal in goats remain unclear. This study examined the ability of M. agalactiae to colonise the ears of goats infected experimentally by the intramammary route. The right mammary glands of 15 lactating goats were inoculated with 10(10) colony forming units (cfu) of M. agalactiae. The goats were randomly assigned to three groups of five animals each and sampled at slaughter at 5, 15 or 45 days post-infection (dpi). A further four goats served as uninfected controls. Right and left ear swabs were collected for detection of M. agalactiae by culture before and after sacrifice. M. agalactiae was detected in 19/20 (95%) ear swabs from goats sampled at 15 and 45dpi, whereas all ear swabs collected before inoculation, ear swabs collected from the group sampled at 5dpi and ear swabs from control goats at the time of sacrifice were negative for M. agalactiae. Blood samples collected at 6, 12, 24, 48 and 72h post-infection for detection of M. agalactiae by culture were also negative. There were differences in the antigenic profiles of isolates recovered from the ears compared to the 7MAG strain used to inoculate the animals and most isolates from the mammary gland, milk and supramammary lymph nodes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

CC chemokine ligand 17 (CCL17/thymus and activation-regulated chemokine: TARC) and CCL22 (macrophage-derived chemokine: MDC) selectively bind to CC chemokine receptor 4 (CCR4). The CCR4 system is considered to be responsible for the pathology of allergic diseases such as atopic dermatitis. To find and develop potential medicines against allergic diseases, we screened an in-house library to search for compounds having a profile as a CCR4 antagonist. From among the screening hits, we focused on 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154), which had been newly synthesized in our laboratory. This compound inhibited the binding of [(125)I]CCL17 to human CCR4-expressing CHO cells with an IC(50) value of 27.7 nM and moreover inhibited CCL17-induced migration of DO11.10 mice-derived T helper 2 cells with an IC(50) value of 1.5 nM in vitro. We then examined the effect of RS-1154 in an ovalbumin-induced ear swelling assay. The ear thickness was decreased by intravenous administration of anti-CCL17 or anti-CCL22 antibodies, suggesting that the CCR4 system is involved in the ear swelling. Though partially, the oral administration of RS-1154 also significantly ameliorated the ear swelling at the doses of 30 and 100 mg/kg. Furthermore, the serum level of interleukin-4 decreased after the administration of RS-1154. In this study, we succeeded in obtaining a newly-synthesized compound, RS-1154, which has a potential to inhibit the chemotaxis of T helper 2 cells in vitro and to ameliorate ovalbumin-induced ear swelling in vivo. These results raise the possibility that RS-1154 or one of derivatives might become a therapeutic agent for atopic dermatitis patients.

The authors report 4 cases of cutaneous lymphoproliferation unusual by their histology and their clinical presentation. Each presented with a history of a slow growing nodule on the ear. Despite the indolent clinical evolution, the histology suggested a high-grade lymphoma. All lesions consisted of a dense, diffuse proliferation of monomorphous medium-sized T cells throughout the dermis and subcutis. There was no epidermotropism and a grenz zone was clearly present in each case. The tumor cells displayed irregular blastlike nuclei, with small nucleoli and clear chromatin and had a CD3+, CD8+, CD4+, TIA1+, granzyme B(-)immunophenotype with a loss of other T-cell antigens. The 3 cases with available material for polymerase chain reaction studies displayed a monoclonal T-cell rearrangement of the T-cell receptor-gamma chain. These cases do not correspond to a recognized cutaneous T-cell lymphoma as described in the recent WHO/EORTC classification. The apparent striking propensity for the ear suggests that they might represent a specific entity. Further cases are needed to confirm this hypothesis. It is important for such indolent lesions to be known to avoid over treatment.

Background: Sand fly saliva has an array of pharmacological and immunomodulatory components, and immunity to saliva protects against Leishmania infection. In the present study, we have studied the immune response against Lutzomyia intermedia saliva, the main vector of Leishmania braziliensis in Brazil, and the effects of saliva pre-exposure on L. braziliensis infection employing an intradermal experimental model., Methodology/principal Findings: BALB/c mice immunized with L. intermedia salivary gland sonicate (SGS) developed a saliva-specific antibody response and a cellular immune response with presence of both IFN-gamma and IL-4. The inflammatory infiltrate observed in SGS-immunized mice was comprised of numerous polymorphonuclear and few mononuclear cells. Mice challenged with live L. braziliensis in the presence of saliva were not protected although lesion development was delayed. The inoculation site and draining lymph node showed continuous parasite replication and low IFN-gamma to IL-4 ratio, indicating that pre-exposure to L. intermedia saliva leads to modulation of the immune response. Furthermore, in an endemic area of cutaneous leishmaniasis, patients with active lesions displayed higher levels of anti-L. intermedia saliva antibodies when compared to individuals with a positive skin test result for Leishmania., Conclusion: These results show that pre-exposure to sand fly saliva plays an important role in the outcome of cutaneous leishmaniasis, in both mice and humans. They emphasize possible hurdles in the development of vaccines based on sand fly saliva and the need to identify and select the individual salivary candidates instead of using whole salivary mixture that may favor a non-protective response.

Introduction: Numerous tests have been developed to help in the diagnosis of the immunomediated inner ear disease (IMIED), although their usefulness is still the subject of some dispute., Material and Method: Studies of cohorts of patients with suspected IMIED have been reviewed. A number of different serological tests were carried out and their response to immunosuppressive therapy was noted., Results: After reviewing 790 articles, the studies analyzed present great heterogeneity in the clinical characteristics of the patients recruited (sudden deafness, fluctuating and rapidly progressive hearing loss, Menière's disease), the inclusion and exclusion criteria, the delay between the diagnosis and the start of medical treatment or the response criteria., Conclusions: The diagnosis of IMIED is based on clinical presentation and response to corticosteroids. At present no test represents the gold standard in the diagnosis of IMIED. Serologic tests can support the diagnosis, but a methodologically more rigorous approach is needed to identify the true clinical importance of these tests for daily practice.

Background/aims: The inner ear can be the target of autoimmune disorders. Recognition of autoimmune inner ear disease is important, as it is one of the very few forms of sensorineural hearing loss (HL) that can be successfully treated by medical therapy. The aim of this study was to evaluate whether the detection of antibodies to myelin protein P0 (MPZ) could be a diagnostic test for inner ear disease of autoimmune cause., Methods: This multicentric prospective study included 129 patients: patients with progressive sensorineural HL or with Menière's disease, together with their control group corresponding to patients with similar symptoms, but of presumably known origin. Detection of antibodies to myelin P0 protein was performed by using western blots. NORMAL: The prevalence of antibodies to myelin P0 protein in patients with rapidly progressive HL was not statistically different from that of the control group corresponding to genetic HL patients (30 versus 28%). In patients with Menière's disease, the prevalence was lower than that of the control group corresponding to patients with benign paroxysmal positional vertigo (5.4 versus 18.7%). No patient with auto-immune disease had antibodies to myelin P0 protein., Conclusions: The sole presence of antibodies to myelin P0 may not be used as a marker of inner ear disease of autoimmune origin.

Syphilis is a well established cause of hearing loss. Sensorineural hearing loss may develop in the congenital or acquired form. The clinical course of the early acquired and late congenital forms are similar: sudden or rapidly progressive bilateral sensorineural hearing loss with mild vestibular symptoms. Cochleovestibular involvement in early acquired syphilis has been related to a basilar meningitis with lymphocytic infiltration of the labyrinth and VIIIth nerve. However, neurosyphilis and inner ear syphilis are not the same disease. Prompt diagnosis and treatment with corticosteroids and penicillin are mandatory to reduce the immune response and fibrosis of the labyrinth and the endolymphatic sac. Unfortunately, early acquired syphilis is frequently overlooked in the differential diagnosis of other forms of sensorineural hearing loss, particularly autoimmune inner ear disease. Given the increasing number of luetic infection cases, especially in immunocompromised patients, this condition should be considered in any sexually active patients affected by sudden hearing loss. Cases of inner ear syphilis are presented. Immunopathology of luetic inner ear infection is discussed and compared with immune disorders of the inner ear.

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.

Background: Cytoplasmic antineutrophil cytoplasmic autoantibodies (cANCA)/proteinase-3(PR3)-ANCA was considered the serologic diagnostic marker for Wegener's granulomatosis (WG). However, Chinese patients with MPO-ANCA positive WG were frequently diagnosed. We now analyze the characteristics of patients with MPO-ANCA positive WG and investigate the difference between patients with MPO-ANCA and PR3-ANCA., Methods: Patients with WG were selected according to both Chapel Hill Consensus Conference definition and American College of Rheumatology (ACR) classification criteria in 500 Chinese patients with ANCA-associated systemic vasculitides. The clinical manifestions were compared between patients with MPO-ANCA and with PR3-ANCA., Results: Eight-nine patients fulfilled the diagnostic criteria of WG: 54/89(60.7%) were MPO-ANCA positive, 34/89(38.2%) were PR3-ANCA positive. Patients with MPO-ANCA were predominantly female compared with patients with PR3-ANCA. Patients with MPO-ANCA also had multisystem involvement. However, the prevalences of arthagia, skin rash, ophthalmic and ear involvement were significantly lower in patients with MPO-ANCA than those in patients with PR3-ANCA (46.3% vs. 70.6%, P < 0.05; 20.4% vs. 44.1%, P < 0.05; 27.8% vs. 58.8%, P < 0.01; 40.7% vs. 67.6%, P < 0.05, respectively). The prevalence of elevated initial serum creatinine was significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA (81.5% vs. 61.8%, chi(2) = 4.20, P < 0.05)., Conclusion: Patients with MPO-ANCA positive WG were not rare in Chinese.

Background B7-1 transgenic mice exhibit exaggerated and persistent contact hypersensitivity responses compared with normal mice. Objective Because B7-1 and B7-2 deliver different costimulatory signals to T cells during antigen presentation, the purpose of this study was to compare B7-1 and B7-2 on keratinocytes and to compare their effects on contact hypersensitivity. Methods Contact hypersensitivity was studied in transgenic mice whose keratinocytes constitutively expressed B7-1, B7-2, or no costimulatory molecules (nontransgenic mice). Results B7-1 transgenic mice, and to a lesser extent B7-2 transgenic mice, developed exaggerated ear swelling responses after sensitization and challenge with haptens such as trinitrochlorobenzene or dinitrofluorobenzene. Ear swelling responses in B7-1 transgenic mice were characterized by the presence of markedly elevated inflammatory cytokine transcripts (IL-6, TNF-alpha, and lymphotoxin beta) as well as IL-10 compared with either B7-2 or nontransgenic mice. Hapten-specific IgE was detected by ELISA in B7-1 transgenic mice but not B7-2 transgenic or nontransgenic mice. Only B7-1 transgenic mice exhibited significant immediate type ear swelling responses to the hapten trinitrochlorobenzene. In addition, their sera can passively transfer cutaneous anaphylaxis to naive C57BL/6 mice, indicating that the hapten-specific IgE was relevant to the immediate ear swelling responses. Conclusion These data suggest that keratinocyte-derived costimulation mediated by B7-1 but not B7-2 results in the emergence of T H 2-lymphocyte immune responses to T H 1 haptens. Because human keratinocytes have been noted to express B7-1-like molecules in certain inflammatory skin diseases, this model may be important in understanding the pathophysiology of T H 2-lymphocyte-mediated skin diseases such as atopic dermatitis.

Intranasal challenge of C57BL/6 mice with Streptococcus pneumoniae serotypes 6B, 14, and 23F produced colonization of the middle ear and NP. Intranasal vaccination with ethanol-killed nonencapsulated cells with adjuvant protected both sites. Of four nontoxic adjuvants tested, the cholera toxin B subunit was most effective and least nonspecifically protective.

Allergy may affect the outer, the middle, or the inner ear. Although the otologic manifestations of allergy are not by themselves diagnostic, the history, including family history and associated symptoms in other target organs, will often help lead to the correct diagnosis and institution of therapy. Patients with significant and chronic symptoms, including those with labyrinthine symptoms of allergy, respond well to specific immunotherapy or dietary elimination.

Autoimmune Inner Ear Disease (AIED) is a clinical syndrome of uncertain pathogenesis. It is associated with bilateral rapidly progressive hearing loss. The hearing loss may be associated with vestibular symptoms. Autoimmunity has been proposed as the pathogenesis of this sort of hearing loss, although the mechanism of the disease is poorly understood. It is well accepted that the endolymphatic sac is an immunocompetent organ and circulating autoantibodies against inner ear antigens have been reported, as have viral antigens in the endolymph, although the sensitivity, specificity, and roles of those antibodies in a disease process are poorly defined. We will describe the clinical aspects of the disease, the histopathology, the immunologic indicators, the types of presentation, both from the audiologic and vestibular point of view, clinical trials for treatment and the follow-up. One of our conclusions is that many of these patients respond favorably to the treatment Methotrexate.

Crude inner ear antigen (CIEAg) can induce autoimmune inner ear disease (AIED) although it is not known which subcomponent of CIEAg is involved. In this study, we investigated the relationship between 3 purified inner ear antigens (31, 42-45 and 60 kD proteins) and AIED, and determined their distribution in normal guinea pig cochlea. Three groups of guinea pigs were immunized with the three inner ear antigens and one group served as a control. The hearing thresholds, serum IgG level and morphological changes in the inner ear were observed. The expression of the three antigens in the cochlea was detected using immunohistochemical techniques. No obvious changes in hearing thresholds or inner ear morphology were observed between the control and 42-45 kD groups. Animals immunized with the 31 or 60 kD proteins showed a significant increase in hearing thresholds (p < 0.05 vs control), accompanied by morphological changes in the inner ear. The serum IgG level was increased significantly (p < 0.05) in all immunized animals. The 31 kD protein was distributed in the cochlear nerve and spiral ganglion, while the 42-45 and 60 kD proteins were distributed widely, being found in the spiral ganglion, organ of Corti, stria vascularis and spiral ligament. These results suggest that two subcomponents of CIEAg (the 31 and 60 kD proteins) may induce AIED independently, that several inner ear antigens may contribute to the pathogenesis of AIED and that the 31 kD protein is of high tissue specificity and may be used as a marker protein for the clinical diagnosis of AIED.

B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11) or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of TH1 cytokine (interferon-gamma) in Peyer's patches and of TH1/TH2 cytokines (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had been fed CTB-CB11. An increase of CD8+ T cells in the Peyer's patches with a decrease of CD8+ T cells in lymph nodes was seen in mice that had been fed CTB-CB11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction.

Objective: To elucidate the relationship between the auricular pseudocyst and the immunological function of patients., Method: The cyst fluid and blood sample had been detected for contents of IgG, IgA, IgM and complement C3 by radial immunodiffusion, immunocomplex (IC) contents by polyethylene glycol turbidimetry in 55 cases, anti-nuclear antibody (ANA) by immuno-fluorescent technique in 23 cases, extractable nuclear antibody (ENA) by immunotransfer technique in 24 cases. The frozen sections of cyst wall tissue of 24 cases had been detected for immunocomplex by immunoenzyme histochemistric method. The reactions were observed separately between the auricle tissue of healthy white rat, human embryo and cyst fluid, serum of patient and normal serum., Result: Contents of IgG, IgA, IgM and C3 in the cyst fluid were lower than the serum significantly (P < 0.01). No IC, ANA and ENA could been found both in serum and cyst fluid, but reactive immunocomplex was discovered on the auricle cartilagous tissue of patient, immunocomplex also be observed on human embryo aurical tissue when it reacted with cyst fluid, but complex hadn't be found when the auricle tissue of white rat and human embryo reacted with serum of patient and normal people., Conclusion: The reason of auricular pseudocyst may be related with the local autoimmune status of patient.

It has been shown that sera from patients with autoimmune inner ear disease contain antibodies to several inner ear antigens. We report here the characterization of the 42-43 kDa protein against which a significant number of patients' sera react strongly. After separation of inner ear proteins from guinea-pig cochleas by SDS-PAGE, the band corresponding to the 42-43 kDa protein was digested with trypsin and the peptide fragments were separated by high-performance liquid chromatography. Two fractions were then subjected to amino acid sequencing by the classical automated Edman degradation. The sequence of a stretch of 15 amino acids of the first fragment was identical to that of amino acids 148-162 of beta-actin. The sequence of the 10 amino acids of the second fragment was also identical to beta-actin. On Western blots, monoclonal antibody directed against beta-actin reacted with the inner ear 42-43 kDa proteins. The serum samples from the patients and the monoclonal antibody reacted with the non-muscle actin used as antigen in Western blotting. Immunoblot analysis of inner ear proteins after two-dimensional gel electrophoresis showed a spot, corresponding to the region of the 43 kDa as compared to the protein standards. On the basis of these data it is concluded that the target 42-43 kDa protein for antibodies in sera of patients with autoimmune inner ear disease is beta-actin, a molecule, which has important and numerous functions inside cells. This is the first report to identify the cytoskeletal protein beta-actin as a candidate autoantigen in autoimmune inner ear disease.

Objective: To elucidate the relationship between the auricular pseudocyst and the systemic and local immunological status., Methods: The cyst fluid and blood samples of 44 cases were collected to measure contents of IgG, IgA, IgM and complement C3 by radial immunodiffusion, the content of immune complex by polyethylene glycol turbidimetry, DNA of cytomegalovirus in the fluid by polymerose chain reaction, anti-nuclear antibody(ANA) by immunofluorescent technique and reactions between samples and frozen sections of healthy white rat., Results: Contents of IgG, IgA, IgM and C3 in the cyst fluid were significantly lower than those in the serum (P < 0.01). No immune complex could be detected in both serum and cyst fluid. No DNA of cytomegalovirus was found in cyst fluid, whereas ANA was discovered. Reactive immunocomplex in the auricular cartilaginous tissue was found in the frozen sections of white rats., Conclusion: The results suggest that auriular pseudocyst may be an autoimmune disease involving the auricle. The possible mechanism may be an accumulation of reactive exudate due to immunoreactions of autologous antibody and auricular tissue.

In various patterns of sensorineural hearing loss including Ménière's disease, which may show improvement in auditory function following immunosuppressive therapy, an isolated autoimmune disease of the inner ear has been postulated. Because of the lack of well-defined diagnostic criteria to identify autoimmune processes within the inner ear and the fact that the human inner ear is one of the few organs of the body not amenable to diagnostic biopsy, there has been great interest in developing animal models that mimic these clinical entities. Previous studies have found evidence that this process might be cell mediated and that the endolymphatic sac functions as an immunodefensive organ for the inner ear. By heterologous immunization of inbred Lewis rats with inner ear tissue, an autoreactive inner-ear-specific T helper cell line was established. After passive transfer of these cells a labyrinthitis was induced in recipient animals. Immunohistochemically, T helper cells were first identified in the cochlea suggesting that this cell type might carry the autoantigenic epitope. Autoantibodies against inner ear tissue were demonstrated in animals with histologically evident labyrinthitis. We conclude that this experimental design can serve as an animal model for cell-mediated autoimmune disease of the inner ear and could be used to explain the etiology of certain types of sensorineural hearing loss such as Ménière's disease. With this approach the identification of the causative autoantigen should be possible and will lead to the development of appropriate clinical tests to diagnose autoimmune diseases of the inner ear in humans.

The cutaneous side-effects of levamisole include non-specific and lichenoid eruptions, fixed drug eruption and, very rarely, cutaneous vasculitis. We describe a distinctive clinical and histological vasculopathy with immunological abnormalities in children with paediatric nephrotic syndrome receiving long-term levamisole treatment. Four boys and one girl were identified. Their average age was 10 years. Levamisole had been used for an average of 24 months. Purpura of the ears was the most common finding corresponding histologically to a vasculopathic reaction pattern ranging from a leucocytoclastic and thrombotic vasculitis to a vascular occlusive disease without true vasculitis but with associated antinuclear, antiphospholipid and anticytoplasmic antibodies. The eruption resolved in all patients 2-3 weeks after the discontinuation of levamisole, but serum autoantibodies persisted for 2-14 months.

Allergy may affect the outer, the middle, or the inner ear. Although the otologic manifestations of allergy are not by themselves diagnostic, the history, including family history and associated symptoms in other target organs, will often help lead to the correct diagnosis and institution of therapy. Patients with significant and chronic symptoms, including those with labyrinthine symptoms of allergy, will respond well to specific immunotherapy and/or dietary elimination.

Objective: This study aimed to evaluate the outcome of long-term hearing benefits of plasmapheresis (PMP) in presumed autoimmune inner ear disease (AIED)., Study Design: The study was a case series, with retrospective chart review, written questionnaire, telephone interview, and follow-up examination., Setting: It was performed in a private practice otology and neurotology referral center., Patients: Sixteen patients (5 males, 11 females) whose symptoms were compatible with the diagnosis of AIED, who underwent PMP, and who had 2-year or later objective follow-up. Age ranged from 8-62 years, with a mean of 40.9 years. Follow-up ranged from 2-12 years, with a mean of 6.7 years., Intervention: Plasmapheresis at one or more times during the active phase of disease., Main Outcome Measure: Stability of hearing, defined according to the American Academy of Otolaryngology-Head and Neck Surgery recommended criteria for reporting hearing results in Meniere's disease, was used as the main outcome measure., Results: Eight (50%) of 16 patients had improved or stable hearing in 1 or both ears. Eleven (39.3%) of 28 ears with measurable hearing pre-PMP were improved or stable. Only 25% of patients required continued use of immunosuppressive drugs., Conclusion: Plasmapheresis may be beneficial as an adjunctive therapy for maintaining hearing in some patients with AIED. Cost and reimbursement factors are major obstacles in the use of this therapy. The overall success rate and individual patient results warrant further study of PMP in the treatment of AIED.

The etiopathogenesis of many inner ear disorders still remains idiopathic. Immunological mechanisms are attracting attention in relation to a number of these diseases. Some cases are believed to be autoimmune in origin. The present study was conducted to determine whether patients with inner ear disorders produce antibodies that may be pathologic to the inner car or result from its damage. Sera from 100 patients with various inner ear disorders were tested for autoantibodies using the indirect immunofluorescence test. Inner ear tissue preparations from healthy guinea pigs were used as antigen substrates. Adequate tissue and serological controls were applied. Two groups of antibodies were detected; antibodies directed against the inner ear tissues (18%) and antibodies directed against different tissue/cellular elements (41%). A wide variety of inner ear antibodies were found, though no common type manifested itself. Meniere's disease was the most common clinical diagnosis in the antibody-positive group.

Data are presented from 15 dogs with aural haematoma. The series included six Labrador retrievers and four golden retrievers and the mean age was 8.0 +/- 3.02 years. Five dogs had evidence of pruritic skin disease and five further cases had other concurrent disease. Haematology and serum biochemistry were normal in 12 and 13 of the 15 dogs, respectively. All dogs were Coombs' negative and serum antinuclear antibody had negative or low titres in all the 11 cases tested. Histopathological examination of biopsies from the affected ears revealed variable degrees of erosion of auricular cartilage with fibrovascular granulation tissue filling the cartilage defects. There was minimal perichondral inflammation. The biopsies were studied by immunohistochemistry for deposition of immunoglobulin G (IgG), immunoglobulin M (IgM) and complement C3. In one dog there was basement membrane zone deposition of IgG and in another there was focal interepithelial deposition of both IgG and IgM. The findings of this study do not support an autoimmune pathogenesis for canine aural haematoma, but suggest that an early immunological event may underlie the observed cartilage erosion.

We have previously shown that a 30,000 Mr protein extracted from guinea pig inner ear tissue is recognized by autoantibodies present in the serum of patients suffering from autoimmune inner ear disease. This protein was localized in the modiolus and in the organ of Corti. We have now identified this protein by a combination of microsequencing and matrix-assisted laser desorption ionization time-of-flight mass spectrometry of its tryptic peptides. A partial sequence of the protein was thereby determined. These data and 2-dimensional gel electrophoresis followed by immunoblotting experiments showed that the 30,000 Mr inner ear antigen is the major peripheral myelin protein Po. This suggests that protein Po may be an important autoantigen in autoimmune inner ear disease.

Immune-mediated inner ear disease, first described by McCabe in 1979, typically presents with an idiopathic, rapidly progressive bilateral sensorineural hearing loss. The course of the hearing loss occurs over weeks to months. It may occur in both sexes and at a variety of ages, but is most common in middle-aged females. It may be accompanied by tinnitus, Meniere's-like vertigo, or more commonly, ataxia or unsteadiness. Approximately 30% of patients will have associated systemic immune-mediated disease. Although refinements in laboratory tests for specific inner ear antigens are being made, and non-specific laboratory indicators of inflammatory or systemic immune disease may be useful in confirming the diagnosis, the most important diagnostic finding is the improvement in hearing seen with a trial of immunosuppressants. This report includes a typical evaluation of the patient with suspected immune-mediated inner ear disease and an illustrative case. Sensorineural hearing loss due to immune-mediated inner ear disease, although unusual as a cause of hearing loss, is important to recognize because early diagnosis and treatment can have a marked effect on the clinical outcome.

In this study, the authors attempted to develop a method of extracting guinea pig inner ear antigens for otoimmunological research, and to investigate the distribution of the antigens in the various structures of the inner ear. The antigens were extracted either from the entire or from various parts of the guinea pig inner ear. These antigens were separated on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Western blot techniques were used to test sera from patients with inner ear disease against guinea pig inner ear protein extracts. It found that the various molecular weight antigens in the inner ear were associated with the different structures of the inner ear. The sera of 37.5% (N = 80) of patients reacted with two bands (30 and 58 kd) of the guinea pig inner ear immunoblots. The 58 kd band was not specific to the inner ear, but instead was also found in the immunoblots of other guinea pig tissues (brain, lung, and liver). This study suggests that the various antigens of interest could be further extracted and purified from the corresponding locations of the inner ear.

To identify the epitope on the type II collagen molecule that induced autoimmune ear disease, electrophysiological and histological studies were carried out in DBA/1J mice immunized with native chick type II collagen (Clln) and cyanogen bromide (CNBr) peptide 1I (CB-I1 peptide) that was cleaved from chicken type II collagen with CNBr digestion. Four months after immunization, three of six Clln-immunized mice and five of six CB-I1 peptide-immunized mice developed moderate hearing loss. No control animals showed hearing loss. The pattern of hearing loss was characteristic of progressive deafness. Furthermore, the immunized mice showed temporal lesions involving atrophy of the Corti organ and degeneration of the spiral ganglion, in proportion to the level of the hearing loss. Because similar inner ear lesions were induced by immunization with Clln and CB-I1 peptide, CB-I1 peptide contains at least one epitope that induces autoimmune inner ear disease in collagen II-induced disease on the chick type II collagen molecule involved in pathogenesis of autoimmune ear disease. CB-I1 peptides were concluded to contain the epitope that induces autoimmune inner ear disease in collagen IIn-induced disease.

The immunoreactivity of sera from patients with rapidly progressive sensorineural hearing loss (SNHL) or Menière's disease with bovine inner ear material was determined using the Western blot technique. Patients with other otologic conditions, autoimmune disorders, or arthritic disorders and age-matched randomly chosen patients with no hearing complaints served as controls. Twenty-two percent of the patients with bilateral rapidly progressive SNHL and 30% of the patients with Menière's disease had antibodies that reacted with a 68 kd antigen in the inner ear material. In the control groups, the incidence of reactivity was 5.0% (P < .001). When the results of this study were compiled with data collected previously, it was found that of 279 patients with bilateral rapidly progressive SNHL, 90 (32%) were positive with the 68 kd protein. Thus, the anti-68 kd antibody may provide a good marker for an immune etiology of these patients' hearing loss.

Donor T lymphocytes injected into the host systemic circulation were observed to infiltrate into the host endolymphatic sac in mice. These findings suggest that the endolymphatic sac, a major immune organ in the inner ear, is supplied with immunocompetent cells from the systemic circulation. This concept is consistent with clinical reports that inner ear disorders accompany certain systemic autoimmune diseases. Bone marrow transplantation to replace autoreactive immunocompetent cells with normal cells should be considered as a potential therapy for inner ear autoimmune diseases and an alternative to conventional treatments.

Basing on the actual world literature authors present opinions concerning methods of healing damages of internal ear caused by immunological processes. The following methods of healing internal ear damages are mentioned above: using of steroids in high doses for a long time, steroids and cytostatic drugs or cytostatic drugs itself (in case of bad toleration) or steroids parallelly with plasmaphoresis (as supporting method) or plasmaphoresis itself.

An immune response directed against type II collagen (CII) has been reported in several autoimmune diseases including the animal models of collagen-induced arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this communication, we have found that T cells from type II collagen-immunized DBA/1-lac could transfer auricular chondritis to naive mice. The T cells from type II collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11 peptide of CII. The CII-specific T cells from H-2q background mice recognize peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By altering certain amino acids within these epitopes, the response of CII-specific TCR to antigen has been increased or abolished. Our results suggest that the lysine residues at positions 129, 141, and 147 in P1, the arginine residue at position 227, and glutamic acid at position 230 in P2 might play an important role in the trimolecular interaction. Ten clonally distinct T cell hybridomas specific for CII have been established from H-2r B10.RIII mice and the beta chains of their TCR have been analyzed. Three subfamilies, V beta 1, V beta 6, and V beta 8, were utilized with dominant expression of V beta 8 (60%). This is quite similar to the pattern found in type II collagen-induced arthritis in H-2q mice. This preferential use of V beta 8 in CIAED implies that an immunotherapy may make it possible to control this autoimmune disease, even in a MHC-diverse situation.

Immune inner ear disease is a relatively new and distinct clinical entity that produces unexplained, rapidly progressive, bilateral sensorineural hearing loss. The diagnosis is based on clinical manifestations, positive immune laboratory testing, and beneficial response to a trial of corticosteroids. Immune laboratory tests are used to confirm a presumptive clinical diagnosis. The two tests most commonly used are the lymphocyte transformation test and Western blot immune assay. The rationale behind these tests is presented, and the role they play in laboratory diagnosis of immune inner ear disease is discussed.

The immune response genes that control the immune response and recognition of 'self' from 'nonself' are closely linked with the human leukocyte antigen (HLA) complex. Sixty-six HLA antigens were typed in 42 Caucasian patients with inner ear diseases of unknown etiology. All of these patients had positive serum antibodies against the inner ear structures as detected by an indirect immunofluorescence assay. Results revealed that none of the 66 HLA antigens was associated with the inner ear diseases. Reviewing results from other studies on HLA association in inner ear diseases shows that the findings are inconsistent with each other. The conclusion that HLA associations occur with inner ear diseases cannot be reached.

In a rechallenge system examining murine contact hypersensitivity to DNFB in BALB/c mice, the reactivity to the specific antigen at the previously responded site and the persistence of an immunological memory were investigated. Flare-up reactions were induced 4 weeks after the first challenge only at the previously responded site by local or systemic administrations of minute quantities of a specific antigen. The intensity of ear swelling was dependent on the quantity of applied antigen at the time of the rechallenge. The local hypersensitivity to the specific antigen observed in the previously responded site and the regional lymph node persisted for at least 1 year. These results suggest that the sensitivity to a specific antigen at the previously responded site is intensified and the immunological memory persists for a long time. This may explain the mechanisms by which chronic contact dermatitis recurs readily at the limited site by exposure to minute quantities of causative antigens.