Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes.

BACKGROUND

Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.

METHODS

We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.

RESULTS

Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (p < 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, p = 0.007) and IFN-γ (HR = 0.26, p = 0.046) may represent biomarkers of disease activity.

CONCLUSION

MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling.