Experimental Immune-Mediated Hearing Loss

Kim, Hwan Jae; Park, Yong Su; Chang, Gi Hong; Yeo, Sang Won

Abstract

BACKGROUND AND OBJECTIVES: In 1979, MaCabe described the autoimmune sensorineural hearing loss generally characterized by bilateral progressive sensorineural hearing loss over weeks to months. He also described steroid responsiveness of heaing loss. Since then, numerous attempts have been tried to investigate autoimmune inner ear disease. But, there is insufficient information concerning pathophysiology and no reliable laboratory tests are available for diagnosis. In this study, we immunized healthy rats with bovine brain antigen, and monitored auditory brainstem response threshold shifts and serum antibody titer especially antibody to 68 kD protein, and observed histologic changes to develop animal model and to investigate pathophysiology of inner ear autoimmunity. MATERIALS & METHODS:We used 15 female Wistar rats weighing 200 g to 250 g. Three of them (as control group) were immunized with bovine serum albumin and the rest were weekly immunized with bovine brain antigen 3 times. After the antigen challenges, animals were sacrificed at 1st, 2nd, 4th or 8th week after collection of serum and ABR test. Hearing was evaluated by ABR prior to each immunization and at 1st, 2nd, 3rd, 4th, 6th or 8th week following immunization. Collected sera were analyzed by Western blotting immunoassay against fresh bovine brain antigen preparation.
RESULTS
On ABR, hearing threshold shifts of 10 to 40 dB were recorded and shifts of greater than 20 dB were recorded in 8 ears (33.3%) of 24 ears. On Western blot assay, a band at 68 kD M.W. was observed with high binding activity at 1st week through 4th week following immunization. Cellular infiltration was observed in the are as adjacent to the spiral modiolar venules in the cochlear modiolus and in the spiral ganglion cells in a scattered pattern.
CONCLUSION
These results suggest that bovine brain antigen can induce autoimmune inner ear disease in experimental animals and that inner ear autoimmunity may play an important role in the development of inner ear disorders and hearing loss.