Autoimmune mouse antibodies recognize multiple antigens proposed in human immune-mediated hearing loss

Hypothesis: Autoimmune diseased mice with hearing loss will have autoantibodies against the various cochlear antigens proposed in clinical autoimmune inner ear disease. Background: Serum antibodies of patients with hearing loss recognize several proteins that are proposed as possible antigenic targets in the ear. This often leads to a clinical diagnosis of autoimmune inner ear disease, although it is not clear how these antibodies cause inner ear disease. Therefore, to better understand the relationship of autoantibodies and ear disease, an examination was made of serum autoantibodies in the MRL/MpJ-Fas^lpr autoimmune mouse with hearing loss. Similar antibody patterns in the mouse would provide an animal model in which to investigate potential autoimmune mechanisms of this clinical ear disorder. Methods: Sera from MRL/MpJ-Fas^lpr autoimmune mice and normal C3H mice were tested by the enzyme-linked immunosorbent assay technique for reactivity against various reported cochlear antigens: heat shock protein 70 (bovine, human, bacterial), laminin, heparan sulfate proteoglycan, cardiolipin, and collagen types II and IV. Results: The autoimmune mouse sera showed significantly greater antibody reactivity against all of the antigens when compared with normal mouse sera. Conclusions: Serum antibodies from autoimmune mice recognized several putative autoantigens reported for patients with hearing loss, suggesting that comparable antigen-antibody mechanisms might be operating. However, the recognition of multiple antigens did not identify any one as being the specific target in autoimmune hearing loss. The correlation of antibodies in the MRL/MpJ-Fas^lpr autoimmune mouse and human studies indicates this animal model should aid further investigations into potential cochlear antigens in autoimmune hearing loss.