Monoclonal antibody induced hearing loss

Nair, Thankam S.; Raphael, Yehoash; Dolan, David F.; Parrett, T; Perlman, Larry S.; Brahmbhatt, Vivek R.; Wang, Yu; Hou, Xiaoming; Ganjei, Gholizadeh; Nuttall, Alfred L.; Altschuler, Richard A.; Carey, Thomas E.

doi:10.1016/0378-5955(94)00194-u

Cited by 36 publications

(41 citation statements)

References 34 publications

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“…A cell-surface location of the IESCA is consistent with KHRI-3 and anti-CTL2 IF staining at the membrane of supporting cells (Fig. 3) (Zajic et al, 1991;Nair et al, 1995Nair et al, , 1997Nair et al, , 1999.…”

Section: Identity Of Ctl2 and The Iesca Defined By Khri-3mentioning

confidence: 68%

“…Two rabbits (R228 and R229) were each immunized four times with 500 g of the synthetic CTL2 peptide (Princeton Biochemicals, Langome, PA). Antisera were tested for approximate antibody titer by ELISAs against the immunizing peptide, as described previously (Zajic et al, 1991;Nair et al, 1995). Protein-G-purified KHRI-3 IgG 1 antibody and protein-A-Sepharose (Pierce)-purified IgG from the rabbit antisera to CTL2 were coupled to cyanogen bromide (CNBr)-activated Sepharose 4B beads (Sigma, St. Louis, MO) in a ratio of 5 mg of antibody to 1 gm of beads.…”

Section: Methodsmentioning

confidence: 99%

“…In the guinea pig organ of Corti, the KHRI-3 antibody binds to supporting cells with a distinctive "wine-glass" pattern. Infusion of purified antibody into the cochlea yields in vivo binding to supporting cells in the organ of Corti that is accompanied by loss of outer hair cells, loss of hearing, and redistribution of the antigen in the regions of hair cell loss (Nair et al, 1995(Nair et al, , 1999. Sera from suspected AHL patients often have antibody that binds to guinea pig inner ear supporting cells with the same distinctive wine-glass staining pattern as that observed with the monoclonal antibody (Disher et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Two groups identified heat shock protein 70 (HSP70) as a candidate target antigen Bloch et al, 1995); however, HSP70 has not held up as a high-probability inner ear target antigen (Billings et al, 1998;Trune et al, 1998;Yeom et al, 2003). We developed monoclonal antibodies to cells isolated from the guinea pig (GP) organ of Corti (Zajic et al, 1991) and observed that hearing loss developed in mice carrying the Kresge Hearing Research Institute-3 (KHRI-3) hybridoma (Nair et al, 1995), provoking us to study this antibody and its antigen in more depth. In the guinea pig organ of Corti, the KHRI-3 antibody binds to supporting cells with a distinctive "wine-glass" pattern.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

Nair¹,

Kozma²,

Hoefling³

et al. 2004

J. Neurosci.

108

133

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The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with its expression on the surface of supporting cells in the inner ear, CTL2 contains 10 predicted membrane-spanning regions with multiple N-glycosylation sites. The 68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the transporter function of this molecule. CTL2 mRNA and protein are abundantly expressed in human inner ear. Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans.

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Section: Identity Of Ctl2 and The Iesca Defined By Khri-3mentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

Nair¹,

Kozma²,

Hoefling³

et al. 2004

J. Neurosci.

108

133

View full text Add to dashboard Cite

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“…Thus, there is a conspicuous lack of direct evidence that HSP-70 Ab's are autonomously pathogenic in ASNHL. Although other studies have shown hearing loss in guinea pigs injected with the KHRI-3 IgG1 mAb generated against cochlear hair cells, the identity of the recognized antigen is currently unknown (14)(15)(16).…”

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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Corticosteroid Response and Supporting Cell Antibody in Autoimmune Hearing Loss

Zeitoun¹,

Beckman²,

Arts³

et al. 2005

Arch Otolaryngol Head Neck Surg

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To determine whether antibodies to supporting cells are associated with response to corticosteroids in patients with autoimmune sensorineural hearing loss. Design: Prospective analysis of antibody to inner-ear antigens. Setting: Collaborating otology practices in Pennsylvania, Michigan, and Indiana. Patients: Sixty-three patients with rapidly progressive unilateral or bilateral sensorineural hearing loss of unknown cause suggestive of autoimmune sensorineural hearing loss. Interventions: Pretreatment audiometry, serum analysis by Western blot (WB) and immunofluorescence (IF) tests, corticosteroid therapy, and follow-up audiometry. Main Outcome Measures: Antibody reactivity and audiogram changes were analyzed for association with response to treatment. Results: More than half of the patients (37/63) had antibodies to both a 68-to 72-kDa protein and to innerear supporting cells, 16 patients had positive results on one assay only, and 10 had negative results on both. Twenty-eight patients improved and 35 did not. The WB findings did not correlate with response. Of the WBpositive patients, 49% (21/43) improved, as did 35% (7/ 20) of the WB-negative patients (P=.30). In contrast, 53% (25/47) of IF-positive patients improved, compared with only 19% (3/16) in the IF-negative group (P = .02). Of those who improved, 89% (25/28) were IF positive. Conclusions: Antibody to an inner-ear supporting cell antigen was significantly associated with hearing improvement after corticosteroid therapy (relative rate, 2.8). Patients with IF-positive serum are nearly 3 times more likely to experience improved hearing with corticosteroid treatment than those who are IF negative. Antibodies to inner-ear supporting cell antigen may have value in diagnosis and treatment of patients with autoimmune sensorineural hearing loss.

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Monoclonal antibody induced hearing loss

Cited by 36 publications

References 34 publications

Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

Identification and Characterization of Choline Transporter-Like Protein 2, an Inner Ear Glycoprotein of 68 and 72 kDa That Is the Target of Antibody-Induced Hearing Loss

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

Corticosteroid Response and Supporting Cell Antibody in Autoimmune Hearing Loss

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