Decreased cochlear DNA receptor staining in MRL.MpJ-Fas(lpr) autoimmune mice with hearing loss

OBJECTIVES: Previous studies of decreased cochlear DNA binding in autoimmune mice suggested that antibodies against a cochlear cell surface DNA receptor cause autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not been determined. Therefore, immunohistochemistry with an anti-DNA receptor antibody was performed on MRL.MpJ-Fas(lpr) (MRL/lpr) autoimmune mice to determine 1) which inner ear structures contain DNA receptors and 2) whether the receptor staining pattern changes as autoimmune disease progresses and hearing thresholds increase. STUDY DESIGN: A prospective study of the progression of hearing loss in autoimmune mice and correlated alterations in immunostaining for the inner ear DNA receptor. METHODS: One group of MRL/lpr mice (n = 10) was allowed to develop autoimmune disease, and auditory brainstem response (ABR) audiometry was performed at 4, 6, and 9 months of age to measure the progression of hearing loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and immediately killed to assess receptor staining before the onset of autoimmune disease and hearing loss. The inner ears from all mice were immunohistochemically stained with an anti-DNA receptor antibody, and a qualitative analysis of the staining of cochlear structures was performed. RESULTS: Auditory brainstem response audiometry revealed a significant 20- to 30-dB elevation of thresholds as systemic disease progressed. Anti-DNA receptor staining was heaviest in the spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both groups showed a similar pattern of staining in these structures. The stria vascularis and hair cells also stained in both groups. However, the stria cells of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas older mice displayed less staining that was confined to the cell membranes. CONCLUSIONS: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune hearing loss was correlated with weaker overall intracellular staining in the stria vascularis and hair cells but increased staining of the cell membranes. This suggested DNA receptors have impaired endocytosis and more receptors remain on the cell membrane, possibly as a result of binding by circulating autoantibodies.     

Female MRL.MpJ-Fas(lpr) autoimmune mice have greater hearing loss than males

Although women make up approximately 60-70% of the patients with autoimmune hearing loss, little is known about the impact of gender on this cochlear disease. To explore this relationship of gender and autoimmune inner ear disease, an evaluation was made of cochlear function in male and female autoimmune MRL.MpJ-Fas(lpr) mice. Autoimmune disease and hearing loss onset occur at 3-4 months of age, so mice were tested with auditory brainstem response audiometry at 3, 6, and 9 months of age to identify potential gender differences in thresholds. Sera also were analyzed for differences in the autoimmune factors of immune complexes, anti-nuclear antibodies, and hematocrits. By 9 months of age the surviving mice showed a dramatic gender difference. Female mice had thresholds 25-45 dB higher than males at 4, 8, and 16 kHz, although male thresholds at 32 kHz had risen sufficiently to be statistically similar to those for females. No gender differences were seen in any of the systemic autoimmune factors. These findings of worse hearing in female autoimmune mice parallel a reported female preponderance in clinical immune hearing disorders. This potential gender influence in autoimmune inner ear disease must be better understood for effective evaluation and treatment of this disorder.     

Mineralocorticoid receptor mediates glucocorticoid treatment effects in the autoimmune mouse ear

The standard treatment for many hearing disorders is glucocorticoid therapy, although the cochlear mechanisms involved in steroid-responsive hearing loss are poorly understood. Cochlear dysfunction in autoimmune mice has recently been shown to be controlled with the mineralocorticoid aldosterone as effectively as with the glucocorticoid prednisolone. Because aldosterone regulates sodium, potassium, and other electrolyte homeostasis, this implied the restoration of hearing with the mineralocorticoid was due to its impact on cochlear ion transport, particularly in the stria vascularis. This also suggested glucocorticoids may be controlling hearing recovery in part through their binding to the mineralocorticoid receptor in addition to their glucocorticoid receptor-mediated anti-inflammatory and immunosuppressive functions. Therefore, the aim of the present study was to better delineate the role of the mineralocorticoid receptor in steroid control of hearing in the autoimmune mouse. Spironolactone, a mineralocorticoid receptor antagonist, was administered to MRL/MpJ-Fas(lpr) autoimmune mice in combination with either aldosterone or prednisolone to compare their hearing and systemic disease with mice that received either steroid alone. ABR thresholds showed either aldosterone or prednisolone alone preserved hearing in the mice, but spironolactone prevented both steroids from maintaining normal cochlear function. This suggested both steroids are preserving hearing through the mineralocorticoid receptor within the ear to regulate endolymph homeostasis. The spironolactone treatment did not block normal glucocorticoid receptor-mediated immune-suppression functions because mice receiving prednisolone, either with or without spironolactone, maintained normal body weights, hematocrits, and serum immune complexes. Thus, reducing systemic autoimmune disease was not sufficient to control hearing if mineralocorticoid receptor-mediated functions were blocked. It was concluded the inner ear mineralocorticoid receptor is a significant target of glucocorticoids and a factor that should be considered in therapeutic treatments for steroid-responsive hearing loss.     

Steroid treatment in young MRL.MpJ-Fas(lpr) autoimmune mice prevents cochlear dysfunction.

Corticosteroid therapy reverses clinical autoimmune sensorineural hearing loss, although little is known of how steroids restore normal auditory function. If suppression of systemic autoimmune processes underlies hearing restoration, then preventing autoimmune symptoms from developing should prevent cochlear dysfunction. MRL. MpJ-Fas(lpr) autoimmune mice were used to test this potential mechanism by initiating oral prednisolone treatment at 6 weeks of age, prior to autoimmune disease and hearing loss onset. The steroid treatment group was given prednisolone in their drinking water, while untreated controls were given tap water. Treatment continued for 7 months with periodic evaluations of cochlear function with auditory brainstem response (ABR) audiometry. Autoimmune mice given the steroid lived longer and did not develop levels of serum immune complexes seen in their untreated controls. Also, their ABR thresholds remained near normal throughout the 7 months of treatment, while untreated controls showed progressive threshold elevations typical for autoimmune disease. This correlation of suppressed systemic autoimmune activity and maintenance of normal cochlear function identifies one potential mechanism for autoimmune hearing loss and hearing restoration with steroid therapy. The autoimmune mouse should serve as a valuable model for future studies of the cochlear mechanisms responsive to steroid treatment in autoimmune hearing loss.     

Autoimmune-mediated sympathetic hearing loss: a case report.

BACKGROUND: Damage to one inner ear is occasionally followed by contralateral sensorineural hearing loss. This has been defined as sympathetic hearing loss. HYPOTHESIS: It is hypothesized that autoimmunity can play a role in the pathogenesis of sympathetic hearing loss. METHODS: A male patient who developed right-sided sympathetic hearing loss at 20 years of age, 11 years after deafness of the left ear caused by a temporal bone fracture, is described. The patient's serum was analyzed for the presence of autoantibodies against inner ear tissues by immunocytochemistry and Western blotting using rat inner ear tissues. The patient's serum was tested specifically for antibodies against heat shock protein 70 by immunodot blot. The presence of autoantibodies known to play a role in systemic autoimmune disease was also examined. RESULTS: Immunocytochemistry on rat temporal bone sections demonstrated autoantibodies in the patient's serum specifically targeted against cochlear outer hair cells. No reactivity of the patient's serum was observed with control tissues including kidney, brain, and liver. Western blotting using homogenized rat cochlear tissues showed that the patient's serum reacted with a 25- and 27-kDa protein. No reactivity was observed with heat shock protein 70 in the immunodot blot analysis. The patient's serum did not contain autoantibodies against antinuclear antibodies, double-stranded DNA, antineutrophil cytoplasmic antibodies, basement membrane, reticulin, intestinal mucosa, muscle, collagen, or mitochondria. CONCLUSION: Observations indicate that this patient suffered sympathetic hearing loss caused by organospecific autoimmunity directed to cochlear outer hair cells.     

Steroid treatment improves cochlear function in the MRL.MpJ-Fas(lpr) autoimmune mouse.

Corticosteroid therapy is used to reverse autoimmune sensorineural hearing loss, although little is known of the mechanism by which this occurs. This has been due to the lack of a suitable animal model with spontaneous hearing loss that is steroid responsive. The present study examined the effects of prednisolone treatment on auditory thresholds in the MRL.MpJ-Fas(lpr) autoimmune mouse to determine its suitability as such a model. Autoimmune mice at 3.5-4. 5 months of age were evaluated by pure-tone auditory brainstem response (ABR) to establish threshold elevations due to the disease. The steroid treatment group was then given prednisolone in their drinking water for 2.5 months, while untreated controls were given tap water. Significantly more steroid treated mice survived to the time of post-treatment ABR evaluation. Half of the steroid treated ears demonstrated either improvement or no change in cochlear function compared to only 25% in the untreated controls. Overall, cochlear thresholds in the untreated controls increased by 14.7 dB, whereas no significant threshold increase was seen in the steroid treated group (4.3 dB) over the treatment period. No qualitative anatomical differences were seen in the ears of those mice surviving to the end of the study. These findings establish the autoimmune mouse as a model for studies of steroid responsive mechanisms within the ear. This could apply to autoimmune sensorineural hearing loss, as well as any hearing disorder for which steroid therapy is recommended.     

Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice

HYPOTHESIS: Although the glucocorticoid prednisone is the standard therapy for autoimmune sensorineural hearing loss, what this hormone does in the ear to restore hearing is not known. MRL/MpJ-Fas(lPr) autoimmune mice consistently have shown only stria vascularis disease, implying that abnormal ion balances in the endolymph underlie cochlear dysfunction. Previously we have shown that hearing loss in these mice is reversed with prednisolone treatment. This, coupled with the complete lack of cochlear inflammation, suggests that the restoration of hearing with prednisolone is due to its sodium transport function and not to its anti-inflammatory or immune suppression effects. Therefore the hypothesis of this study was that the mineralocorticoid aldosterone, which only increases sodium transport, would be as effective as prednisolone in reversing autoimmune hearing loss. STUDY DESIGN: MRL/MpJ-Fas(lPr) autoimmune mice were treated with either prednisolone or aldosterone to compare steroid effects on auditory brainstem response (ABR) thresholds and stria morphology. METHODS: After baseline ABR audiometry, autoimmune mice were given prednisolone (5 mg/kg per day), aldosterone (15 microg/kg per day), or water in their drinking bottles. After 2 months of treatment the ABR thresholds were remeasured, and ears collected for histological examination. RESULTS: The untreated controls showed continued elevation of ABR thresholds and edematous stria. However, thresholds in most steroid mice were improved or unchanged and their stria morphology improved, particularly with aldosterone treatment. CONCLUSIONS: Restoration of hearing with steroid treatment is due to increased sodium transport to re-establish cochlear ionic balances. Aldosterone therapy may offer advantages over prednisone for long-term management of not only autoimmune hearing loss, but also other forms of nonimmune-related deafness for which steroids are currently prescribed.     

Aldosterone and prednisolone control of cochlear function in MRL/MpJ-Fas(lpr) autoimmune mice

Recently this laboratory showed aldosterone, a mineralocorticoid that only enhances sodium transport, was as effective as the glucocorticoid prednisolone in restoring cochlear function in autoimmune mice. To further test this relationship between sodium transport and autoimmune hearing loss, dosage comparisons were made of prednisolone and aldosterone control of the auditory dysfunction in autoimmune MRL/MpJ-Fas(lpr) mice. Mice were tested at 2 months of age to establish baseline auditory brainstem response (ABR) thresholds, hematocrit, serum immune complexes, and anti-nuclear antibodies. Mice were then given different doses of prednisolone or aldosterone in their drinking water for 2 months. After the treatment period, most untreated water controls showed elevation of ABR thresholds due to the ongoing autoimmune disease. However, the steroid groups had significantly more mice with improved or unchanged thresholds. Both steroids improved stria vascularis morphology, although aldosterone appeared to be more effective. The immune suppressive prednisolone caused a dose-related improvement in levels of serum immune complexes and hematocrit, hallmarks of systemic autoimmune disease. Aldosterone, which has no immune suppressive function, did not alter systemic disease. The comparable efficacy of prednisolone and aldosterone in restoring auditory function suggests steroid reversal of autoimmune hearing loss in mice is due to increasing stria vascularis sodium transport and not suppression of systemic autoimmune reactions.     

Bone marrow cells as an origin of immune-mediated hearing loss

The MRL/lpr mouse, which is homozygous for the recessive lpr genes and has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, exhibits severe lymphadenopathy and develops systemic lupus erythematosus (SLE)-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of reconstituting severe combined immunodeficient (SCID) mice with MRL/lpr bone marrow on the development of SHL. These mice normally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology did, indeed, occur following transfer of MRL/lpr bone marrow into SCID mice. These findings suggest that the development of SHL and cochlear pathology observed in MRL/lpr mice and in SCID mice receiving MRL/lpr bone marrow are the result of bone marrow defects rather than the result of a problem intrinsic to the cochlea.     

系统性红斑狼疮患者血清中抗内耳组织自身抗体的免疫转印分析

为了解系统性红斑狼疮（ＳＬＥ）患者血清中是否存在抗内耳组织交叉反应性自身抗体，提取制备豚鼠内耳膜迷路抗原，应用免疫转印技术，对１８例尚无听力下降的ＳＬＥ患者进行分析。结果发现：１６例（占８８．９％）患者血清中存在着抗内耳组织交叉反应性自身抗体，而１１例正常对照血清全部为阴性。提示内耳也可能是ＳＬＥ多器官受损的靶器官之一。     

Detection of humoral immune response to inner ear proteins in patients with sensorineural hearing loss]

BACKGROUND: The precise mechanism of inner ear disease is still unknown. An autoimmune reaction could be one of several possible pathogenic factors involved in progressive sensorineural hearing loss. Heat shock protein 70 is suggested to play an important role in the development of autoimmune diseases. The aim of this study is the investigation of humoral immune reactivity to inner ear components in patients with sensorineural hearing loss. METHODS: The presence of antibodies to inner ear components was determined by immuno-blotting extracted bovine or human inner ear proteins. Study groups consisted of patients with idiopathic progressive sensorineural hearing loss (group A), patients with Menière's disease (group B), patients with sudden hearing loss (group C), patients with otosclerosis (group D), patients with Cogan's disease (group E), and individuals without hearing problems (group F). RESULTS: 40% of the patients with progressive sensorineural hearing loss showed reactivity against a 68-kDa protein extracted from bovine inner ear. In contrast to this, only 5% of healthy individuals and 10% with Menière's disease showed reactivity against the 68-kDa protein from bovine inner ear or against bovine heat shock protein 70. Some of the patients who showed reactivity against bovine inner ear proteins were tested with human inner ear and human heat shock protein 70; all of these showed reactivity. Approximately 6% of the patients with sudden hearing loss (group C), otosclerosis (group D), and Cogan's disease (group E) showed reactivity to inner ear proteins. A non-specific humoral immune reaction against inner ear proteins with molecular weights of 30, 40, 50, 60, and 220 kDa was observed in all patients. DISCUSSION: These results indicate a humoral immune reactivity against heat shock protein 70, which might be responsible for the pathogenesis of progressive sensorineural hearing loss.     

同种内耳抗原免疫致聋豚鼠的子代内耳功能和形态学观察

目的观察自身免疫性感音神经性聋(autoimmune sensorineural hearing loss，ASHL)母鼠所产子代内耳听觉和前庭生理功能、病理形态学的变化，初步探讨母鼠体内针对内耳组织抗原免疫反应是否可以造成子代的内耳损伤。方法同种内耳抗原(homogeneous inner ear antigens，HIEAg)持续免疫孕豚鼠，采用耳蜗电图(包括听神经复合动作电位)、总和直流电位、耳蜗微音器电位和眼震电图仪(记录自发性和冷热空气试验)测试母鼠和子鼠的听觉和前庭功能，并检测针对HIEAg的血清特异性体液和细胞免疫反应，采用火棉胶切片和HE染色，光镜观察内耳病理组织学改变。结果ASHL母鼠所产子鼠中，部分(3／7)出现听觉损伤，并发现其血清中特异性抗体水平升高，内耳出现免疫炎性病理损伤。非ASHL母鼠和对照组母鼠所产子代未见明显异常。结论ASHL雌鼠所产子代可出现感音神经性聋，其内耳损伤和功能障碍极可能与针对内耳组织的自身免疫反应(尤其是体液免疫)有关。     

Bone marrow cells as an origin of immune-mediated hearing loss

The MRL/lpr mouse, which is homozygous for the recessive lpr genes and has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, exhibits severe lymphadenopathy and develops systemic lupus erythematosus (SLE)-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of reconstituting severe combined immunodeficient (SCID) mice with MRL/lpr bone marrow on the development of SHL. These mice normally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology did, indeed, occur following transfer of MRL/lpr bone marrow into SCID mice. These findings suggest that the development of SHL and cochlear pathology observed in MRL/lpr mice and in SCID mice receiving MRL/lpr bone marrow are the result of bone marrow defects rather than the result of a problem intrinsic to the cochlea.     

Glucocorticoid impact on cochlear function and systemic side effects in autoimmune C3.MRL-Faslpr and normal C3H/HeJ mice

Glucocorticoids are effective in reversing hearing loss, but their severe side effects limit long term management of many ear disorders. A clearer understanding of these side effects is critical for prolonged therapeutic control of hearing and vestibular dysfunction. Therefore, this study characterized the impact of the glucocorticoid prednisolone on cochlear dysfunction and systemic organ systems in C3.MRL-Fas(lpr) autoimmune mice and their normal C3H/HeJ parent strain. Following 3 months of treatment, autoimmune mice had better auditory thresholds and improved hematocrits, anti-nuclear antibodies, and immune complexes. Steroid treatment also lowered body and spleen weights, both of which rise with systemic autoimmune disease. Steroid treatment of the normal C3H/HeJ mice significantly elevated their blood hematocrits and lowered their body and spleen weights to abnormal levels. Thus, systemic autoimmune disease and its related hearing loss in C3.MRL-Fas(lpr) mice are steroid-responsive, but normal hemopoiesis and organ functions can be significantly compromised. This mouse model may be useful for studies of the detrimental side effects of steroid treatments for hearing loss.     

Spironolactone blocks glucocorticoid-mediated hearing preservation in autoimmune mice

HYPOTHESIS: Although autoimmune sensorineural hearing loss can be effectively treated with corticosteroids, little is known about how these drugs affect cochlear function. MRL/MpJ-Faslpr autoimmune mice treated with a mineralocorticoid (aldosterone) have previously been shown to have hearing improvement equal to those treated with a glucocorticoid (prednisolone). This suggested that the restoration of hearing with steroids was the result of an effect on sodium transport rather than an antiinflammatory or immunosuppressive role. We hypothesized that corticosteroids reverse autoimmune hearing loss through the mineralocorticoid receptor and that blocking the mineralocorticoid receptor will prevent glucocorticoid effects. METHODS: Spironolactone, a mineralocorticoid receptor antagonist, was administered to MRL/MpJ-Faslpr autoimmune mice alone or in combination with corticosteroids. The four treatment groups were: spironolactone, spironolactone + aldosterone, spironolactone + prednisolone, and untreated water controls. Auditory brainstem response (ABR) thresholds were recorded before and during treatment (2, 3, and 4 mo) to measure the effect of steroids on hearing decline. RESULTS: Hearing in spironolactone and spironolactone + prednisolone mice showed progressive decline in hearing similar to water controls. The hearing was preserved in spironolactone + aldosterone mice, presumably as a result of the fact that aldosterone has a higher affinity for the mineralocorticoid receptor than spironolactone. Thus, aldosterone was able to maintain cochlear function with autoimmune disease progression, similar to previous reports of aldosterone treatment effects. CONCLUSIONS: Spironolactone effectively blocked prednisolone from improving hearing in MRL/MpJ-Faslpr autoimmune mice. This offers evidence that the inner ear mineralocorticoid receptor is the therapeutic target for corticosteroids used to treat autoimmune and sudden sensorineural hearing loss. Pharmacologic treatments that selectively target the mineralocorticoid receptor may provide greater clinical benefit with fewer systemic side effects than prednisone in patients with autoimmune sensorineural hearing loss.     

Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural hearing loss

In order to clarify the possible mechanism of hearing loss in immune-mediated sensorineural hearing loss, basic research needed includes animal model studies. In the present investigation, we examined hearing thresholds and cochlear histologies of the MRL/lpr mouse which is now well-known as a model for pathology consistent with systemic lupus erythematosis (SLE). Present findings demonstrated that there were no statistically significant differences in auditory brainstem response (ABR) thresholds between 4- to 6-week-old “young” and 20- to 25-week-old “old” MRL mice. These differences were not sex-dependent. Under light microscopy, there were no abnormal morphological findings in the cochleas of either young or old MRL mice. With immunohistochemistry, mouse IgG was detected around the capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG level of the MRL mice significantly decreased after predonisolone (PSL) administration. However, expression of mouse IgG in the stria vascularis was not observed in the MRL mice after PSL administration. From these results, we speculate that the hearing of the MRL mouse does not always deteriorate, and the deposition of mouse IgG on the capillary wall in the stria vascularis is not a sufficient factor to induce hearing loss. At this point, we conclude that the MRL mouse should not be considered a useful model for immune-mediated sensorineural hearing loss. Received: 22 July 1997 / Accepted: 4 December 1997     

Frequency of cochlear enhancement on magnetic resonance imaging in patients with autoimmune sensorineural hearing loss

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) scans for enhancement of inner ear structures of patients with sensorineural hearing loss and documented antibodies to the 68-kd inner ear antigen. STUDY DESIGN: Retrospective case review with reexamination of MRI scans. SETTING: Outpatient office. PATIENTS: Thirty-five patients with autoimmune sensorineural hearing loss defined by audiograms documenting a sensorineural hearing deficit in one or both ears and the presence of an anti-inner ear antibody (68-kd band) in serum samples who underwent precontrast and postcontrast T1-weighted axial and coronal MRI scans of the inner ear, which were performed concurrently with the hearing loss. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Frequency and intensity of cochlear enhancement on MRI scans. RESULTS: One patient demonstrated +2 cochlear enhancement. However, that finding was thought to represent postoperative inflammatory change. CONCLUSION: No correlation was found between the presence of antibodies to inner ear antigen in patients with hearing loss and cochlear enhancement on MRI scans.     

自身免疫性内耳病的实验研究

用同种异体内耳抗原免疫豚鼠，观察听阈、血清免疫学、形态学及免疫病理学的改变，结果发现部分豚鼠ＡＰ（Ｎ＿１）反应阈明显升高、血清中出现抗内耳自身抗体，且表现有膜迷路积水、蜗轴血管炎、螺旋神经元细胞空泡变性、细胞数减少，特别是部分动物蜗轴血管和血管纹毛细血管内皮有ＩｇＧ沉积。提示通过这种实验方法可在部分动物成功地建立实验性自身免疫性内耳病动物模型。此外，就该模型与该病临床表现的相似性进行了比较。     

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.     

不同内耳组织抗原免疫致自身免疫性感音神经性聋的研究

目的：探讨不同内耳组织抗原免疫所致内耳主要病理损伤部位和听力障碍类型。方法：采用同种螺旋韧带（ＳＬ）、基底膜（ＢＭ）、螺旋神经节（ＳＧ）组织抗原免疫豚鼠，观察内耳组织病理改变和听觉功能变化。结果：ＳＬＡｇ和ＢＭＡｇ免疫组主要表现耳蜗微音器电位阈值升高和复聪现象，以及蜗管内和血管纹的免疫炎性病理改变；ＳＧＡｇ免疫组主要表现听神经复合动作电位阈值升高和幅值降低，内耳病理变化主要位于蜗轴血管及周围和ＳＧ