Relevant Research of Inflammatory Cytokines Spectrum in Peripheral Blood of Sudden Hearing Loss.

OBJECTIVE: To investigate whether there is a correlation between the inflammatory state and the pathogenesis and clinical features of sudden hearing loss (SHL) by studying the expression of inflammation-related cytokines in the peripheral blood of patients with SHL. METHODS: In this work, we analyzed the cytokine profiles of 48 analytes in 38 patients with SHL compared to 38 healthy donors using a multiplex immunoassay. This study used appropriate statistical methods to screen for inflammatory cytokines associated with the pathogenesis of SHL, to analyze their network correlation, and to analyze the relationship between clinical features of SHL and inflammatory cytokines. RESULTS: Several cytokines, including CTACK, Eotaxin, HGF, INF-α2, IFN-ß, IL-1ß, IL-1ra, IL-2Rα, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12(p40), IL-13, MIG, ß-NGF, SCF, and TNF-α, exhibited significantly higher levels in the peripheral blood of the SHL group compared to the control group. An inflammatory network composed of multiple cytokines, including IL-1ß, is a risk factor for the development of SHL. CONCLUSION: This study identified several inflammatory cytokines with elevated expression, which may be linked with the onset of SHL. The results of this study also provide a basis for the theoretical hypothesis of inflammation in SHL. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3293-3301, 2024.

Increased incidence of unilateral sudden sensorineural hearing loss in patients with hematological malignancies requiring hematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) may dramatically alter the immunity of a recipient. Transient immunodeficiency that occurs before and after HSCT could be associated with the development of sudden sensorineural hearing loss (SSNHL), which is presumed to be often due to viral aetiology. We found an incidence of SSNHL of 29.4 per 10,000 person-years in patients receiving HSCT, 12-fold higher than reported for background population incidence. Development of SSNHL tended to cluster early after diagnosis of haematological malignancies, rather than around date of treatment with HSCT. Increased risk of unilateral SSNHL in patients with haematological malignancy may relate to underlying disease rather than treatment.

Prestin autoantibodies screening in idiopathic sudden sensorineural hearing loss.

OBJECTIVES: To define the clinical association of serum prestin autoantibodies and their impact on prognosis, as specific serum diagnostic markers in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). DESIGN: Sera from 63 patients with ISSNHL were screened prospectively for the presence of prestin autoantibodies by an enzyme-linked immunosorbent assay (Elisa) test. Serum was assayed for anti-prestin IgG antibodies using recombinant human prestin (SLC26 A5). Demographic, clinical, and audiometric variables were analyzed. RESULTS: Two patients (3.17%) had demonstrable anti-prestin antibodies in serum (exact 95% CI: -1.16% to 7.5%). No statistically significant association was found between prestin autoantibodies and demographic or audiologic parameters. CONCLUSIONS: This preliminary and novel study does not support the presence of an active humoral immune reaction against prestin in ISSNHL.

The Role of Autoimmunity in the Pathogenesis of Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSHL) is a clinically common acute symptom in otolaryngology. Although the incidence of SSHL has increased around the world in recent years, the etiology of the disease is still unclear. It has been reported that infections, ototoxic drugs, membrane labyrinth rupture, carcinomas, circulatory system diseases, autoimmune diseases, brain lesions, mental diseases, congenital or inherited diseases, and so on, are all risk factors for SSHL. Here, we discuss the autoimmune mechanisms behind SSHL, which might be induced by type II-IV allergic reactions. We also introduce the main immunosuppressive medications that have been used to treat SSHL, which will help us to identify potential targets for immune therapy.

Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss using second-generation enzyme immunoassay: A retrospective, multi-institutional investigation in Hokkaido, Japan.

OBJECTIVE: Although elevated anti-mumps IgM antibody levels were reported in 5.7%-7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit. METHODS: This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated. RESULTS: Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p=0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively; no significant difference was seen in these data (p=0.4519). CONCLUSION: The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.

Identification of evidence for autoimmune pathology of bilateral sudden sensorineural hearing loss using proteomic analysis.

Sudden sensorineural hearing loss (S-SNHL) is an inner ear disorder with an abrupt hearing loss occurring <3days. The pathologic mechanism of the disease remains unclear, although autoimmunity has been regarded as one of the suggested causes, especially in bilateral form. In this study, we aimed to provide evidence for the involvement of autoimmunity in bilateral S-SNHL using proteomic approaches such as ProtoArray®, western blotting, immunoprecipitation, and liquid column mass spectrometry for mass screening of candidate antigens and autoantibodies based on the hypothesis that multiple autoantibodies and target antigens must exist in order for autoimmune bilateral S-SNHL to develop. As the final outcome, we have proven the involvement of autoimmunity in the disease, and investigated the existence of circulating autoantibodies and candidate antigens. These findings could provide basic evidence necessary for the development of diagnostic biomarkers as well as the understanding of the pathological mechanisms underlying bilateral S-SNHL. S-SNHL: sudden sensorineural hearing loss; LC-MS: liquid chromatography-mass spectrometry; MS: mass spectrometry; autoAb: autoantibody; 1-DE: one-dimensional electrophoresis.

Can unilateral, progressive or sudden hearing loss be immune-mediated in origin?

OBJECTIVE: The aim of the present study was to demonstrate that the positivity of nonspecific immunological tests could be found not only in bilateral hearing loss but also in unilateral cases, either sudden or progressive. METHOD: An observational case series study included subjects suffering from unilateral or bilateral, sudden or progressive, symmetric or asymmetric sensorineural hearing loss (SNHL). All the patients underwent pure tone audiometry and the following battery of blood exams: anti-nuclear antibody (ANA), extractable nuclear antigen (ENA) antibody screening, anti-thyroperoxidase (anti-TPO), anti-thyroglobulin and anti-smooth muscle antibody (ASMA). RESULTS: The positivity to nonspecific immunological test was found in nearly 70% of the study groups. ASMA and ANA were found to be present in both bilateral and unilateral cases, without statistical difference. Considering the correlation between positivity/negativity and systemic autoimmune pathologies, in the bilateral forms of hearing loss, a high incidence of thyroid pathologies has been identified, with a higher percentage of systemic autoimmune diseases in respect to the normal population. CONCLUSIONS: The nonspecific autoimmune tests are worth to be performed also when SNHL is not bilateral and progressive, since an immunological mechanism could also underlie unilateral and sudden SNHL cases.

The neutrophil-to-lymphocyte ratio in children with sudden sensorineural hearing loss: a retrospective study.

CONCLUSION: The elevated neutrophil-to-lymphocyte ratio (NLR) value in children with sudden sensorineural hearing loss (SSNHL) would suggest the inflammatory etiology of pediatric SSNHL. The results of this study may suggest NLR value can be used as a useful indicator, which is associated with the disease severity in pediatric SSNHL. OBJECTIVES: This study aimed to elucidate any clues of inflammatory etiology, which might be related with the development of pediatric SSNHL, using calculated NLR. METHODS: Forty-six patients aged younger than 19 years, who were admitted to the hospital with the diagnosis of SSNHL, were included in the study. Forty-six healthy children were matched as control group according to their propensity score. The complete blood cell count, calculated NLR, platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) were compared. The relationship between NLR and the initial hearing level was also investigated. RESULTS: The mean NLR value was 2.86 ± 2.58 in the SSNHL group, whereas the mean NLR value was 1.63 ± 0.87 in the control group. The mean NLR value of the SSNHL children was significantly higher than that of the control group (p = .023). There was a positive correlation between the NLR value and initial hearing level (r = .312, p = .037).

Changes of the complement system and rheological indicators after therapy with rheohemapheresis.

INTRODUCTION: In the last 10 years, many studies have been published on the role of the complement system in microcirculation disorders. However, as for the changes of complement components after rheohemapheresis, there is still a lack of detailed data in the literature. Complement changes may play an important role in pathogenesis of some microcirculation disorders, such as age-related macular degeneration and acute hearing loss. The objective of this study was to investigate the effect of rheohemapheresis on the basic complement pathways. PATIENTS AND METHODS: 32 patients were treated with rheohemapheresis, including 16 patients (10 men and 6 women) for age-related macular degeneration (AMD), mean age 69.7 ± 6.06 years (range 62-87 years) and 16 patients (11 men and 5 women) aged 56.4 ± 11.5 (range 34-73 years) for acute hearing loss. RESULTS: Rheohemapheresis led to a significant drop of all three complement-activation pathways in both groups of patients. Moreover, complement factor H was also reduced. CONCLUSION: The observed reduction in all three basic complement activation pathways after rheohemapheresis could be clinically important. The search continues both to find substances which influence complement systems and to develop more effective new drugs that require less frequent administration and that provide improved intraocular therapy for AMD patients.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: novel markers for diagnosis and prognosis in patients with idiopathic sudden sensorineural hearing loss.

BACKGROUND: We aim to provide useful evidence about the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with idiopathic sudden sensorineural hearing loss (ISSNHL) and its possibility of emerging as a cheap, reliable, and independent prognostic marker of ISSNHL. METHODS: 348 patients diagnosed with ISSNHL were included in our retrospective data analysis. Blood samples and the hearing assessments of the patients were carried out. Then, the patients were divided into 2 groups as "recovered" and "unrecovered" according to their response to the treatment. RESULTS: Both mean NLR and PLR values of the ISSNHL patients were significantly higher than the control group (both P < 0.001). The NLR value was 5.98 ± 4.22 in the unrecovered group and 3.50 ± 3.38 in the recovered group (P < 0.001). After adjustment in a binary logistic regression model, only NLR value was associated with the recovery of ISSNHL (P = 0.001). DISCUSSION: We demonstrated for the first time that NLR and PLR values were significantly high in ISSNHL patients. Also the NLR level might be taken into account as a novel potential marker to predict the patients' prognosis in terms of recovery.

Increased neutrophil-lymphocyte ratio in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The aim of this study was to determine whether neutrophil-lymphocyte ratio (NLR) levels are elevated in patients with idiopathic sudden sensorineural hearing loss (ISSHL) compared with healthy controls. Moreover, we aimed to find out whether there is a correlation between NLR levels and the severity of hearing loss. MATERIALS AND METHODS: The study group consisted of 40 subjects with ISSHL and 40 control subjects with no evidence of ear pathology. Severity of hearing loss in the ISSHL patients was classified as mild (<40 dB loss for any frequency), moderate (up to 80 dB), and severe (profound, >80 dB). RESULTS: The mean ± SD NLR values were 5.53 ± 1.72 in the ISHHL patients and 2.73 ± 0.81 in the control group. The mean NLR values in the patients with ISHHL were significantly higher than in the control group (P = 0.0001). The mean ± SD NLR values in the patients with mild (group A), moderate (group B), and severe (group C) sensorineural hearing loss were 5.53 ± 1.72, 5.29 ± 1.81, and 5.82 ± 1.72, respectively. The mean NLR values in the patients with severe sensorineural hearing loss were significantly higher than in the other groups (P = 0.0001). Nevertheless, there was no correlation between NLR values and severity of hearing loss. CONCLUSIONS: There is no previous study that investigated the association between NLR and ISSHL in the literature. High NLR values in ISSHL patients may be a predictor of other ishemic conditions such as coronary or cerebral ischemia. Thus, the otorhinolaryngologist would then refer the patient to cardiology and then neurology specialists for the appropriate examinations.

Expression of autoantibodies in patients with sudden sensorineural hearing loss.

OBJECTIVES: The aim of this study was to establish the expression rate of autoimmunity in patients with sudden sensorineural hearing loss and to determine whether a positive marker is associated with a higher rate of hearing recovery after steroid treatment. METHODS: A prospective study was performed on 137 patients who experienced sudden sensorineural hearing loss and underwent immunoserologic investigations. Autoantibodies evaluated on the day of admission included anti-double-stranded DNA, rheumatoid factor, antiphospholipid immunoglobulins G and M, antinuclear antibody, and complements C3 and C4. RESULTS: Of 137 patients, 75 were male and 62 were female (mean age, 45.1 years). Hearing loss was found on the left side in 61 patients and on the right side in 76 patients. Elevation of at least 1 autoantibody or abnormal complement levels were found in 80 patients (58%), and abnormalities of 2 or more antibodies were found in 28 (20%). There were no statistically significant correlations between autoantibody abnormalities and age, initial hearing level, or positive treatment response. CONCLUSIONS: There is no clear evidence of a correlation between autoimmunity and hearing improvement in patients with autoantibody abnormalities. A high (but not significant) expression rate of autoantibody abnormality and complement level was seen in patients with sudden sensorineural hearing loss.

Lyme disease associated with sudden sensorineural hearing loss: case report and literature review.

OBJECTIVE: Is sudden sensorineural hearing loss associated with Lyme disease in adults? STUDY DESIGN: A retrospective case report and a systematic literature search in PubMed and Embase were performed. RESULTS: We describe a patient presenting with sudden sensorineural hearing loss, followed by a facial paralysis, which could be attributed to Lyme disease confirmed by positive serology and a positive immunoblot. She was successfully treated with ceftriaxone, with recovery of the facial paralysis, although no recovery of the hearing loss was observed. A systematic literature search resulted in 4 relevant and valid articles revealing that confirmed positive serology for Borrelia burgdorferi varies from 0% to 21.3%, suggesting active Lyme disease as a cause in patients with sudden sensorineural hearing loss. Two studies demonstrated a significantly higher incidence of confirmed positive serology for Borrelia burgdorferi as compared with the incidence in the general local population. CONCLUSION: Literature suggests that sudden sensorineural hearing loss may coincide with Borrelia burgdorferi infection. A higher incidence of confirmed positive serology for Borrelia burgdorferi in patients with sudden deafness seems to be depending on the country and on the tests used to confirm Lyme disease. This should be taken into account if serologic testing for Lyme disease in patients with sudden deafness is considered.

The role of allergy in the etiopathogenesis of idiopathic sudden sensorineural hearing loss.

To evaluate the role of allergy in the etiopathogenesis of sudden hearing loss using cytokine profile, allergic parameters, and lymphocyte subgroups, a total of 31 patients aged between 30 and 62 years (mean age: 42.48 ± 15.86 years) with the diagnosis of sudden hearing loss were enrolled in the study between 2008 and 2011. The control group comprised 30 age-matched adult subjects accepted as clinically healthy individuals living in the same region with comparable socioeconomic parameters. The patient and the control group were questioned for history of allergy. Lymphocyte subgroups in the peripheral blood were evaluated using Becton-Dickinson monoclonal CD4, CD8, CD19, and CD23 antibodies. In the patient and control groups, the levels of IFN- γ, IL4, IL10, and total IgE were measured and compared between the groups. Skin test was used for detection of inhaler allergens in the patient and the control groups, and specific IgE tests were performed using the RAST method for food allergens. The Spearman's rho correlation, the unpaired t test, the Mann-Whitney U test, and the Shapiro-Wilk test were used to determine the differences between the groups. The limit for statistical significance was p < 0.05. When the patient and the control group were compared, the differences between CD4, CD23, IL4, IL10, and IgE were statistically significant. On analyses of the patients' serum samples, strongly positive correlations were determined between IgE and CD23, IL10, IL4; IL4 and IL10, CD23, CD4; IL10 and CD23, CD4 (Spearman rho, p = 0.000), while a weakly positive correlation was found between IgE and CD4 (Spearman rho, p = 0.020). A correlation between IFN-γ and CD4 was weakly negative (Spearman rho, p = 0.040). The total IgE levels were estimated to be above the normal reference ranges (0-100 IU/ml) in 25.8 % of the cases in the patient group. History of allergy was found in 61.9 % of the patients. The results of this study substantiate the role of allergy in the etiopathogenesis of sudden hearing loss. We think that during the diagnostic work-up of these patients allergy should be interrogated seriously, necessary tests should be performed, and allergy should be considered in the decision-making process of the treatment of sudden hearing loss.

Proinflammatory cytokine IL-1 ß polymorphisms in sudden sensorineural hearing loss.

The cause and pathogenesis of sudden sensorineural hearing loss (SSNHL) remain unknown. IL-1ß is one of the most powerful inflammatory cytokines. The aim of this study was to evaluate the relationships between interleukin-1 ß (IL-1ß) gene polymorphisms (-511 C/T and +3953 C/T) in patients with SSNHL. One hundred two patients affected by SSNHL and 595 controls were genotyped for IL-1ß gene polymorphisms. The polymorphisms were analyzed by polymerase chain reaction amplification and DNA fragment separation via electrophoresis. Compared to controls, the IL-1ß (+3953) T allele increased the relative risk of SSNHL in subjects with IL-1ß (-511) TT genotype (p = 0.022, OR = 9.111, 95% CI = 1.441-57.618). In this study, polymorphisms in the IL-1ß -511 and IL-1ß +3953 loci were assessed for evidence of association with SSNHL. From this assessment, a significant difference in carriage of both the IL-1ß -511 T allele and the IL-1ß +3953 T allele was observed between SSNHL and controls. This suggests that the IL-1ß -511 and +3953 loci may play an important role in the etiopathogenesis of SSNHL.

No evidence for the diagnostic value of Borrelia serology in patients with sudden hearing loss.

In this evidence-based case report, we address the following clinical question: What is the predictive value of serological testing for Borrelia for diagnosing neuroborreliosis in patients with sudden sensorineural hearing loss? We searched for relevant articles in PubMed, Embase, and Web of Science. We retrieved 49 unique publications and screened the title and abstract of these articles for relevance. We included 2 of 12 studies initially considered relevant to answer our question. These 2 studies reported a seroprevalence of antibodies against Borrelia of 16% in patients with sudden sensorineural hearing loss (SHL) as compared with 13.5% in the general population, but in neither patients with definite neuroborreliosis were they found. To date, there is no evidence regarding the added value of routine diagnostic serologic testing for Borrelia in diagnosing neuroborreliosis in patients with sudden SHL. Neuroborreliosis seems to be a rare cause of sudden SHL, and routine screening of patients for borrelia antibodies in serum should therefore not be recommended.

Apheresis as rescue therapy in a severe case of sudden hearing loss.

A 23-year-old man complained of progressive left ear hearing loss and tinnitus and was unsuccessfully treated with steroids and mannitol. Four months later he presented with sudden, severe, asymmetrical, bilateral sensorineural hearing loss. The results of the laboratory workup were normal except for antinuclear autoantibodies. Auditory brain stem responses showed absent peak and interpeak latencies on both sides. The combination of plasma exchange with high doses of steroids resulted in a definite improvement. Plasmapheresis combined with steroid administration can be used as second-line therapy in idiopathic, sudden sensorineural hearing loss.

Proinflammatory and proadhesive activation of lymphocytes and macrophages in sudden sensorineural hearing loss.

Even though sudden sensorineural hearing loss (SHL) is a quite frequent disease, the pathogenetic processes leading to it are widely unknown. There is increasing evidence that immunomodulatory cells, especially T lymphocytes, might be involved. Twelve patients with acute SHL and 12 healthy, age-matched individuals were included in this study. In addition to routine blood parameters, plasma levels of tumor necrosis factor alpha (TNF-α), soluble CD40 (sCD40) and sCD40 ligand (sCD40L) were determined by ELISA. Moreover, peripheral blood mononuclear cells were isolated by Ficoll density gradient. Afterwards, in subpopulations--identified by CD14 (monocytes), CD68 (macrophages), CD3 (T lymphocytes) or CD19 (B lymphocytes) immunoreactivity--proinflammatory (CD40, TNF-α or cyclooxygenase-2) and proadhesive (CD38) proteins were measured by 2-color fluorescence-activated cell sorter analyses. In comparison with healthy individuals, patients with acute SHL revealed elevated plasma levels of sCD40 and sCD40L and a significantly decreased percentage (36%) of lymphocytes, especially of T lymphocytes (28%). Additionally, in patients with acute SHL the percentage of proinflammatory CD40, TNF-α, cyclooxygenase-2 or CD38-positive T or B lymphocytes was significantly increased. Our data suggest an enhanced extravasation of proadhesive and proinflammatory lymphocytes from the peripheral circulation, which may contribute to SHL disease induction as well as progression and, thus, may be suggested as a novel therapeutical target.