title: Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.
abstract: Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Kresge Hearing Research Institute, Ann Arbor 48109-0506, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Disher
authors.forename: A
authors.initials: A
authors.lastname: Ramakrishnan
authors.forename: T S
authors.initials: TS
authors.lastname: Nair
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
authors.forename: S A
authors.initials: SA
authors.lastname: Telian
authors.forename: H A
authors.initials: HA
authors.lastname: Arts
authors.forename: R T
authors.initials: RT
authors.lastname: Sataloff
authors.forename: R A
authors.initials: RA
authors.lastname: Altschuler
authors.forename: Y
authors.initials: Y
authors.lastname: Raphael
authors.forename: T E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D007758:Ear, Inner / Q000276:immunology*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000276:immunology*; D006801:Humans; D008970:Molecular Weight
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens