Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease

Abstract

Abstract Meniere disease (MD) is an inner ear disorder associated with genetic and environmental factors. Several triggers may induce an inflammatory response that may persist over time, leading to a chronic inflammatory process. This study aims to determine if the inflammatory state observed in some MD patients is mediated by allergy or autoinflammation. A 2-year longitudinal study including 72 patients was designed to track levels of cytokines and chemokines in plasma samples. We used discriminant and trajectory analyses to define functional clusters. Furthermore, THP-1 cells were treated with MD patients’ plasma and NaCl to study their capacity to polarize to M1 or M2 macrophages, and qPCR was used to study the upstream events leading to cytokine release. We identified 4 groups of patients according to their cytokine levels. First, an autoimmune group with high TNF-α levels (19%). An allergic phenotype (24%) with elevated IgE and the capacity to polarize macrophages into M2. The third with an autoinflammatory phenotype had increased IL-1β (14%) activated through CASP1 and NLRP3. The last group had low levels of cytokines (42%). Most individuals remained in the same group according to their cytokine levels over time; interestingly, 36% of patients with an allergic profile also showed high levels of IL-1β. We characterized 2 immunophenotypes according to cytokines and IgE levels. The first may drive an allergic reaction led by IgE and classical allergy-related cytokines. A second group of patients seems to be mediated by the production of IL-1β and the inflammasome pathway.