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INCREASED FREQUENCIES OF COCHLIN-SPECIFIC T CELLS IN PATIENTS WITH AUTOIMMUNE SENSORINEURAL HEARING LOSS
Moo Jin Baek1, Kyung Wook Heo1, Gordon B. Hughes2,Vincent K. Tuohy3
1Department of Otolaryngology, Inje University, Busan Paik Hospital,Busan, Korea/2 Head and Neck Institute, Cleveland Clinic, Cleveland,OH, USA/3Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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OBJECTIVES: Autoimmune etiopathologic events have long been suspected in Autoimmune Sensorineural Hearing Loss (ASNHL), but inner ear specific antigens capable of targeting T cell autoreactivity have not been identified in ASNHL. In this study, we examined the responsiveness of T cells in patients with ASNHL using inner ear specific antigen and to disclose possible mechanisms of ASNHL.■
METHODS: We generated recombinant human cochlin and used it to determine the frequencies of IFN-γ and IL-5 producing T cells in peripheral blood mononuclear cells(PBMC) from 8 patientswith ASNHL, 8 normal hearing control using Enzyme Linked ImmunoSpot (ELISPOT) assay. Antigen specificity controls include wells containing a 1:20 dilution of tetanus toxoid, 25 or 200 mg/ml of OVA or 1:1000 dilution of tuberculin PPD. Sera from 8 ASNHL, 8 normal hearing and 8 other hearing loss control subjects were tested by direct ELISA for cochlin Ab titer.■
RESULTS: The frequencies of IFN-γ producing T cell were significantly higher in patients than control group(472.22±64/1x106 vs 118.20±23.8/1x106 PBMC) in response to 100 mg/ml of human recombinant cochlin(p=0.0001). The frequencies of IL-5 producing Tcell also showed significant differences between two groups( 68.65±25.12/1x106 vs 8.41±2.3/1x106 PBMC) in response to cochlin(p=0.03). No differences were observed in response to 10 mg/ml anti-CD3 and 1:1000 dilution of PPD. ASNHL patients also showed significantly elevated cochlin-specific serum Ab titer compared with both normal hearing age and sex matched control subjects and control with noise and/or age-related hearing loss.■
CONCLUSIONS: Our study is the first to show T cell responsivness 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.