Interferon-γ production to inner ear antigens by T cells from patients with autoimmune sensorineural hearing loss

Lorenz, Robert R.; Solares, C. Arturo; Williams, Paul; Sikora, J.; Pelfrey, Clara M.; Hughes, Gordon B.; Tuohy, Vincent K.

doi:10.1016/s0165-5728(02)00190-x

Cited by 52 publications

(35 citation statements)

References 25 publications

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“…The molecular mechanisms behind the clinically observed effect of response and regain of hearing with glucocorticoid treatment are also unknown. Vari-ous cytokines have been implicated in IM-SNHL, such as interleukin (IL)-1␤, 2 interferon (IFN)-␥, 3 and tumor necrosis factor (TNF; formerly known as tumor necrosis factor ␣). 4 Several clinical trials have been conducted in this patient population with immunemodulating agents such as methotrexate, 5 etanercept, 4,6,7 and infliximab, 8 all with limited success.…”

Section: Arch Otolaryngol Head Neckmentioning

confidence: 99%

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Svrakic¹,

Pathak²,

Goldofsky³

et al. 2012

Arch Otolaryngol Head Neck Surg

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Section: Arch Otolaryngol Head Neckmentioning

confidence: 99%

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Svrakic¹,

Pathak²,

Goldofsky³

et al. 2012

Arch Otolaryngol Head Neck Surg

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“…PBMCs from ASNHL patients have been shown to elicit increased inhibition of leukocyte migration (17), increased proliferation (18), and have increased frequencies of IFN-γ-secreting T cells in response to human inner ear homogenate (19). The involvement of T cells in ASNHL is supported by animal studies showing cochlear pathology and/or hearing loss following immunization of guinea pigs with inner ear homogenate (7,(20)(21)(22) and following adoptive transfer of Lewis rats with T cell lines specific for inner ear homogenate (23,24).…”

Section: Introductionmentioning

confidence: 99%

Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides

Solares¹,

Edling²,

Johnson³

et al. 2004

J. Clin. Invest.

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Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear–specific proteins cochlin and β-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131–150 or β-tectorin 71–90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4+ T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell–mediated organ-specific autoimmune disorder of the inner ear

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“…ELISPOT assays were performed as previously described (24). Briefly, PBMC were separated by centrifugation on Ficoll-Paque (Amersham Biosciences) and the leukocyte fraction was washed and resuspended at 3 ϫ 10 6 cells/ml HL-1 medium (Cambrex) supplemented with L-glutamine, penicillin, streptomycin, HEPES buffer (Invitrogen Life Technologies), and 5% autologous serum.…”

Section: Elispot Assaysmentioning

confidence: 99%

“…We have previously shown that ASNHL subjects have increased frequencies of IFN-␥-producing T cells capable of responding to human inner ear homogenate (24). Despite its ubiquitous use in ASNHL studies, inner ear homogenate is essentially an uncharacterized assortment of a variety of Ags, each at undefined and different concentrations.…”

Section: Production Of Recombinant Human Cochlinmentioning

confidence: 99%

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

Baek

Park

Johnson

et al. 2006

The Journal of Immunology

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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-γ (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.

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Interferon-γ production to inner ear antigens by T cells from patients with autoimmune sensorineural hearing loss

Cited by 52 publications

References 25 publications

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides

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

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