title: Increased frequencies of cochlin-specific T cells in patients with autoimmune sensorineural hearing loss.
abstract: Autoimmune sensorineural hearing loss (ASNHL) is the most common cause of sudden hearing loss in adults. Although autoimmune etiopathogenic events have long been suspected in ASNHL, inner ear-specific Ags capable of targeting T cell autoreactivity have not been identified in ASNHL. In this study, we show by ELISPOT analysis that compared with normal hearing age- and sex-matched control subjects, ASNHL patients have significantly higher frequencies of circulating T cells producing either IFN-gamma (p = 0.0001) or IL-5 (p = 0.03) in response to recombinant human cochlin, the most abundant inner ear protein. In some patients, cochlin responsiveness involved both CD4+ and CD8+ T cells whereas other patients showed cochlin responsiveness confined to CD8+ T cells. ASNHL patients also showed significantly elevated cochlin-specific serum Ab titers compared with both normal hearing age- and sex-matched control subjects and patients with noise- and/or age-related hearing loss (p < 0.05 at all dilutions tested through 1/2048). Our study is the first to show T cell responsiveness to an inner ear-specific protein in ASNHL patients, and implicates cochlin as a prominent target Ag for mediating autoimmune inner ear inflammation and hearing loss.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Moo-Jin
authors.initials: MJ
authors.lastname: Baek
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Park
authors.forename: Justin M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Cengiz Z
authors.initials: CZ
authors.lastname: Altuntas
authors.forename: Daniel
authors.initials: D
authors.lastname: Jane-Wit
authors.forename: Ritika
authors.initials: R
authors.lastname: Jaini
authors.forename: C Arturo
authors.initials: CA
authors.lastname: Solares
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Thomas
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Ball
authors.forename: Nahid G
authors.initials: NG
authors.lastname: Robertson
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Hughes
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Tuohy
mesh_terms: D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016326:Extracellular Matrix Proteins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: C110668:COCH protein, human; D018984:Epitopes, T-Lymphocyte; D016326:Extracellular Matrix Proteins; D011506:Proteins; D011994:Recombinant Proteins