Research Project
7325555
[unreadable] DESCRIPTION (Provided by applicant): Autoimmune hearing loss (AHL) is a subset of sensorineural hearing loss (SNHL) in which there is a sudden onset, or rapidly progressing and/or fluctuating hearing loss that often progresses to bilateral involvement and devastating profound hearing impairment. This is a treatable disorder if diagnosed early; however, no accurate diagnostic test for AHL exists. The development of an accurate test depends on the identification of target antigens. Multiple lines of evidence implicate antibodies to a 68 kDa antigen in AHL. Measurement of these autoantibodies will help physicians properly identify AHL patients and thereby contribute to prompt and proper administration of treatment. Moreover, modifying treatment based on monitoring antibody levels should prevent unnecessary toxicity from the immunosuppressive drugs commonly used to treat AHL. An accurate diagnostic test for AHL will considerably reduce the morbidity and socioeconomic burden associated with diagnosis, treatment and consequences of disease progression in the affected population. Current tests available for diagnosis of AHL are compromised by low sensitivity and specificity. For lack of a better diagnostic tool, Western blot for hsp 70 is currently the most widely used test. There is an absolute need for a precise test to aid physicians treating patients with idiopathic hearing loss and the AHL subset. Recently, our team has identified the 68kDa antigen as choline transporter-like protein 2 (CTL2). This prominent and abundant protein is expressed on the surface of inner ear supporting cells (IESC). Monoclonal antibodies against CTL2 have been shown to induce hearing loss in an experimental guinea pig model. Preliminary studies indicate CTL2 reactive antibodies may be a proximal cause of autoimmune deafness and can be used as a marker for diagnosis of AHL in humans. Monoclonal antibodies directed against CTL2 bind to IESC with a distinctive "wineglass" pattern as evidenced by in vitro immunofluorescence. Patients with AHL frequently have antibodies in the serum that bind to IESC with the same distinctive pattern as anti-CTL2 monoclonal antibodies. We have demonstrated that patients exhibiting such patterns of antibody binding are more likely to respond to treatment with corticosteroids. We propose to develop a simple, reliable, high throughput test to detect anti-CTL2 antibodies in patients with rapidly progressive hearing loss. We postulate that detection of these antibodies will improve sensitivity and specificity significantly. The proposed CTL2 ELISA represents a significant advance in technology to support diagnosis of AHL. This assay will outperform any other test commercially available for this intended use. Relevance of Research to the Public Health: The CTL2 ELISA will fulfill the needs of patients, physicians and the marketplace for an assay to help determine the course of treatment and monitor response to therapy. This will result in decreased morbidity, improved outcomes and minimize economic burden of the affected population. Furthermore, acceptance of the CTL2 ELISA as a valid and reliable aid for diagnosis of AHL will greatly expand the market for serological testing. Idiopathic Hearing Loss is a subset of Sensorineural Hearing Loss (SNHL), a disorder affecting millions of Americans and representing one of the most common and severe disabilities. Patients with Idiopathic Hearing Loss are often suspected of suffering from Autoimmune Hearing Loss, a treatable condition if diagnosed early, and proscribed immunosuppressive treatment. Current diagnostic methods are inadequate to support proper diagnosis AHL; our team proposes to develop a simple, yet precise test to meet this need. [unreadable] [unreadable] [unreadable]
