Mechanisms of Inflammation and Divergent Immune Response in Meniere Disease

Meniere Disease (MD) is a chronic inner ear disorder marked by recurrent episodes of vertigo, sensorineural hearing loss, tinnitus, and aural fullness. Approximately 60–70% of MD cases are sporadic, and increasing evidence supports a significant role for immune-mediated mechanisms in their pathogenesis. This review provides a comprehensive analysis of current evidence on the immunological underpinnings of sporadic MD and explores how these processes give rise to distinct immunophenotypes. Furthermore, in this review, we propose an immunological framework to complement existing clinical diagnostic criteria, enabling more precise classification and personalized management of MD based on immune phenotypes. Research support the concept that MD represents a spectrum of disorders rather than a single disease, comprising at least three distinct immune phenotypes: (1) a T helper 2 (Th2) cytokine–mediated subtype with an allergic-like inflammation; (2) an autoinflammatory subtype characterized by elevated levels of interleukin (IL)-1β; and (3) a subtype associated with autoimmune and/or autoinflammatory comorbidities involving other organs beyond the inner ear. Understanding these phenotypes holds promise for improving diagnostic accuracy and guiding targeted therapeutic strategies in MD. A better understanding of the immune phenotypes in sporadic MD can elucidate promising biomarkers for drug discovery and clinical interventions.