Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease: A longitudinal study
Lidia Frejo, Francisca E. Cara, Marisa Flook, Paula Robles-Bolívar, Alba Escalera‐Balsera, María Alharilla Montilla-Ibáñez, Emilio Domínguez‐Durán, Marta Martínez-Martínez, Patricia Perez‐Carpena, José A. López‐Escámez
Abstract
BACKGROUND: Meniere disease (MD), an inner ear disorder influenced by genetic and environmental factors, potentially leads to chronic inflammation. This study evaluates whether inflammation in MD patients is driven by allergy or autoinflammation. METHODS: 2-year longitudinal study. Cytokine and chemokine levels were measured in plasma from 72 patients. Functional clusters were identified using weighted-based discriminant and km3d trajectory analyses. THP-1 cells were exposed to patients' plasma to assess macrophage polarization, and qPCR analyzed upstream cytokine release events. RESULTS: Four groups were identified: 1) Autoimmune (20 %) with high TNF-α (p = 0.0004); 2) Allergic (25 %) with elevated IgE (p < 0.0001) and M2 polarization; 3) Autoinflammatory (13 %) with increased IL-1β (p < 0.0001), activated via CASP1/NLRP3; 4) Low cytokine levels (42 %; cytokines in Q1). Group stability was observed, with 36 % of allergic patients also showing high IL-1β. CONCLUSION: Identified immunophenotypes, allergy-driven IgE responses, and IL-1β-mediated autoinflammation indicate that targeting inflammation with biomarkers could optimize MD treatment and outcomes.