Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profiles in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early-onset MD (EOMD, 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL,1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p = 0.004) and a higher prevalence of migraine than LOMD (p = 0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3, and CXCL4 were different between patients with MD or migraine and controls.

Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1β into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 $$\times$$× 10⁻⁶) and IGLV3-21 (p = 6.28 $$\times$$× 10⁻³), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1β with up-regulation of IL6 (p = 7.65 $$\times$$× 10⁻⁸) and INHBA (p = 3.39 $$\times$$× 10⁻⁷) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8⁺ T cells.

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (n= 9545), several of them in hearing loss genes, such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

Congenital cytomegalovirus (CMV) infection induces a clinical syndrome usually associated with hearing loss. However, the effect of acquired CVM infection in adults and children has not been clearly defined. The objective of this review is to critically appraise scientific evidence regarding the association of acquired CMV infection with postnatal hearing loss or tinnitus. A systematic review of records reporting sensorineural hearing loss (SNHL) or tinnitus and acquired CMV infection including articles published in English was performed. Search strategy was limited to human studies with acquired CMV infection. After screening and quality assessment, nine studies involving 1528 individuals fulfilled the inclusion criteria. A total of 14% of patients with SNHL showed evidence of previous exposure to CMV, while in individuals without SNHL (controls) the percentage rose up to 19.3%. SNHL was reported as unilateral or bilateral in 15.3%, and not specified in 84.7% of cases. The degree of SNHL ranged from mild to profound for both children and adults. None of the records reported tinnitus. The prevalence of children or adults with acquired SNHL with a confirmed acquired CMV infection by Polymerase Chain Reaction (PCR) or IgM anti-CMV antibodies is low. Phenotyping of patients with acquired CMV infection was limited to hearing loss by pure tone audiometry and no additional audiological testing was performed in most of the studies. Additional symptoms deserve more attention, including episodic vertigo or tinnitus, since some patients with the clinical spectrum of Meniere Disease could result from a CMV latent infection.

Background Meniere Disease (MD) is an inner ear syndrome, characterized by sensorineural hearing loss associated with episodes of vertigo, tinnitus, and aural fullness. The pathological mechanism leading to sporadic MD is still poorly understood, however an inflammatory response seems to be involved in some patients with MD. Methods We performed mass cytometry immunoprofiling on peripheral blood from MD patients and controls to decipher an immune signature associated with the syndrome. Results We have identified two clusters of individuals according to the single cell cytokine profile. These clusters presented differences in immune cell population abundance, including a reduction of CD56^dim NK-cells, and changes in cytokine expression with a different response to bacterial and fungal antigens. Moreover, we observe a difference in the levels of IgE between these two clusters. Conclusions Our results support a systemic inflammatory response in some MD patients that show an allergic phenotype, which could benefit from personalized IL-4 blockers. Immunoprofiling of patients with MD may lead to a better understanding of endotypes of the disease.

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed in MD. Here we performed whole genome bisulfite sequencing in 14 MD patients and 6 healthy controls, with the aim of identifying a MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (N= 9,545), several of them in hearing loss genes such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including 2 UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows to distinguish between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.