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Increased Frequencies of Cochlin-Specific T Cells in Patients with Autoimmune Sensorineural Hearing Loss¹

Moo-Jin Baek^2,*,, Hyun-Min Park^3,*,, Justin M. Johnson^*, Cengiz Z. Altuntas^*,, Daniel Jane-wit^*, Ritika Jaini^*, C. Arturo Solares, Dawn M. Thomas, Edward J. Ball, Nahid G. Robertson^¶, Cynthia C. Morton^¶, Gordon B. Hughes and Vincent K. Tuohy^4,*,

^* Department of Immunology, Lerner Research Institute, Head and Neck Institute, and Allogen Laboratories, Cleveland Clinic, Cleveland, OH 44195; Department of Biology, Cleveland State University, Cleveland, OH 44115; and ^¶ Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

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- (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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Deafness Research Foundation (New York, NY); the Samuel Rosenthal Foundation and the Milton and Charlotte Kramer Foundation (Cleveland, OH); the Triple-T Foundation (Chardon, OH); and National Institutes of Health Grants DC-006422 (to V.K.T.) and DC-003402 (to C.C.M.).

² Current address: Department of Otolaryngology-Head and Neck Surgery, Inje University, Pusan, Paik Hospital, Kaekum-Dong, Pusanjin-gu, Pusan City, South Korea.

³ Current address: Mirae ENT Clinic, 617 Shinsa Dong, Kangnam Gu, Seoul, South Korea.

⁴ Address correspondence and reprint requests to Dr. Vincent K. Tuohy, Department of Immunology, Cleveland Clinic, Lerner Research Institute, NB30, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail address: tuohyv{at}ccf.org

⁵ Abbreviations used in this paper: ASNHL, autoimmune sensorineural hearing loss; HSP, heat shock protein; dB, decibel; WDS, word discrimination score; OHL, other hearing loss; PPD, purified protein derivative; PTA, pure tone average; PVDF, polyvinylidene difluoride.