Autoimmune inner ear disease represents one of the few reversible causes of sensorineural hearing loss. This project is designed to explore the fundamental mechanisms involved in the pathogenesis of autoimmune inner ear disease. The current clinical classification of autoimmune inner ear disease likely represents a heterogeneous group of disorders which include organ specific autoimmune reactions against cochlear antigens as well as nonspecific autoimmune mechanisms, as are found in multisystemic, organ nonspecific autoimmune diseases (e.g. systemic lupus erythematosis/SLE). Important information concerning this disease entity has been gleaned from the study of animal models. However, critical information is still lacking concerning the role of cell mediated immunity, the nature of immune reactions that result in cochlear pathology, and the specific cochlear structures involved in autoimmune reactions. This lack of knowledge has impeded the development of diagnostic and therapeutic protocals for this disease entity. These studies will incorporate two murine animal models, one of organ specific autoimmune ear disease that will be developed utilizing the techniques established by the sponsor, an the MRL-1pr/1pr mouse, a model of SLE manifesting cochlear pathology that has been studied by the candidate. The role of the T helper cell, which is thought to orchestrate both organ specific and organ nonspecific autoimmune reactions, will be evaluated in the proposed models using lymphoblastogenesis assays & in vivo treatment of animals with anti-CD4 monoclonal antibodies. The possible spontaneous occurrence of anticochlear antibodies in the MRL/1pr (Lupus) mouse will be analyzed using Western Blot assays. The specific nature and cellular composition of the immune reaction resulting in organ specific & organ nonspecific autoimmune inner ear disease will be evaluated utilizing immunohistochemical techniques. Lastly, attempts will be made to contribute to the identification of cochlear antigen(s) subject to autoimmune attack by assessing T helper cell blastogenesis in response to specific cochlear antigens isolated utilizing SDS gel electrophoresis. It is expected that the results of these investigations concerning the immunopathogenesis of autoimmune inner ear disease can be applied to human studies for the development of sensitive and specific diagnostic tools as well as specific treatment protocals.
