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Exploring Immune-Mediated Hearing Loss

Howard P. House, MD Memorial Lectureship for Advances in Otology
2:30 pm, Today
New Orleans Theater B

Effectively distinguishing the biologic and clinical differences of autoimmune inner ear disease (AIED) and autoinflammatory disease is critical in treating and even recovering a patient’s sensorineural hearing loss. Andrea Vambutas, MD, will explore the role and treatments for both when she delivers this afternoon’s Howard P. House, MD Memorial Lecture For Advances in Otology. Dr. Vambutas is the Chair of Otolaryngology at New York’s Long Island Jewish Medical Center and an investigator at the Feinstein Institute for Medical Research.

Autoinflammatory diseases affect the immune system (monocyte/macrophage mediated) that are distinct from autoimmune disease. They are capable of inducing sensorineural hearing loss. Autoinflammatory diseases are a relatively new class of inflammatory diseases without clear diagnostic markers, making a diagnosis difficult, Dr. Vambutas said. In fact, she said some diseases previously classified as autoimmune are now considered autoinflammatory, such as gout and Bechets disease. The same is true for some diseases previously considered to be autoimmune. They are now considered to have features of autoimmune and autoinflammatory diseases, such as rheumatoid arthritis
and possibly AIED.

“In both autoimmune and autoinflammatory immune-mediated hearing loss, the patient may experience an acute decline in one or both ears triggered by unknown stimuli,” Dr. Vambutas said. “Timely treatment may permit recovery of some or all of the sensorineural hearing loss. These are diseases of exclusion, and both necessitate screening by imaging to rule out either an inner ear malformation or retrocochlear pathology (i.e., a vestibular schwannoma).”

According to Dr. Vambutas, there are key biologic and clinical features of the two forms of disease that affect hearing. For example, autoinflammatory disease produces excessive interleukin-1 (IL-1) and no autoantibodies. Commercial assays for IL-1 in the blood are not sensitive enough for clinical use. Conversely, AIED has been characterized as disease of the adaptive immune system (T-cell mediated) and some patients  produce rare autoantibodies, although no pathogenic role has been ascribed to these autoantibodies.

According to Dr. Vambutas, the standard of care therapy for AIED is corticosteroids, and 70 percent of patients diagnosed with AIED typically respond well to this treatment. However, that responsiveness to corticosteroids is lost over time. Dr. Vambutas’ most recent research indicates that patients who are corticosteroid-resistant express higher levels of IL-1 in their plasma as compared to corticosteroid-responsive patients. Her team recently completed a small open label trial of anakinra (an IL-1 antagonist) in corticosteroid-resistant AIED patients. Although it appears promising, to date, placebo-controlled studies have yet to be completed.

Autoinflammatory diseases are treated with IL-1 antagonists such as anakinra or canakinumab, she said. Given that corticosteroid-resistant AIED patients responded to anakinra is suggestive that AIED has features of both an autoimmune and autoinflammatory disease.

Otolaryngologists have limited knowledge in deciphering the relative contribution of autoimmune and autoinflammatory disease to immune-mediated hearing losses, Dr. Vambutas said. In particular, the inability to access the human cochlea for biopsy and the lack of durable biologic markers of disease have resulted in the difficulty in deciphering the contribution of autoimmune and autoinflammatory disease to immune-mediated hearing loss.

“Given that AIED patients typically do not have afflicted first-degree relatives, pure monogenic autoinflammatory diseases such as Muckle Wells Syndrome  (which classically has an autosomal dominant inheritance) are less likely to be misconstrued as AIED,” she said. “However, these rare autoinflammatory diseases may provide insight into a mechanism for the development of sensorineural hearing loss from excessive IL-1 release in the development of AIED and other immune-mediated hearing losses. This may possibly result in a new biologic therapy for those patients who have stopped responding to corticosteroids.”