Steroid Resistant Autoimmune Inner Ear Disease: An Autoinflammatory Disease Instead? (171.28)

Abstract

Abstract Autoimmune Inner Ear Disease (AIED) is characterized by bilateral, fluctuating sensorineural hearing loss that has periods of exacerbation triggered by unknown stimuli. We have previously shown that IL-1β is aberrantly expressed in steroid unresponsive AIED patients. These patients exhibit low titer antibodies to mixed molds, at dilutions 1:256 (p<0.005) and 1:512 (p < 0.05) and the inner ear protein, cochlin at dilution 1:256 (p < 0.05), compared to control subjects. PBMC exposure to mold induces an up-regulation of IL-1β mRNA expression, enhanced IL-1β secretion and the generation of IL-17 expressing cells. Mold enriched T-cell cultures from AIED patients showed a five-fold induction of IL-17 producing cells in response to cochlin, suggesting that AIED patients share cross-reactive epitope(s). These results suggest that AIED may, in fact, be better characterized as an auto-inflammatory disease rather than autoimmune, as dysregulation of IL-1β and low-titer autoantibodies are observed in these patients. To further investigate the hypothesis that these patients have autoinflammatory disease, we asked whether LPS alone would be sufficient to induce IL-1β or whether the second stimulus of ATP was necessary. Monocytes from AIED patients secrete higher levels of IL-1β in response to LPS alone than healthy controls, and that the addition of ATP fails to augment IL-1β secretion. Further studies are underway to characterize the inflammasome defect in these patients.