Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Nair TS

PROVIDER: S-EPMC6730453 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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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.

Nair Thankam S TS Kozma Kelley E KE Hoefling Nickoleta L NL Kommareddi Pavan K PK Ueda Yo Y Gong Tzy-Wen TW Lomax Margaret I MI Lansford Christopher D CD Telian Steven A SA Satar Bulent B Arts H Alexander HA El-Kashlan Hussam K HK Berryhill Wayne E WE Raphael Yehoash Y Carey Thomas E TE

The Journal of neuroscience : the official journal of the Society for Neuroscience 20040201 7

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 ...[more]

PMID: 14973250

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Project description:Although recent advances in magnetic resonance imaging (MRI) techniques have contributed to the detection of tiny lesions in the internal auditory canal (IAC) that may be responsible for sudden sensorineural hearing loss (SSNHL), there have been relatively few studies on the clinical characteristics of intra-labyrinthine hemorrhage (ILH) and labyrinthitis versus those regarding IAC tumors. Our purpose was to investigate the frequency of those IAC lesions on MRI and their clinical characteristics. Initial MRIs of 200 patients with SSNHL (93 men, 107 women; mean age = 48.61 years, range: 18-84 years), as well as detailed clinical histories, audiological examinations, and thyroid function, lipid battery, and serological tests (for viral agents and autoimmune disease), were performed. All patients were hospitalized at the time of diagnosis of SSNHL and were administered the same treatment protocol. Patients were divided into idiopathic and secondary groups according to their MRI results. After discharge, they underwent follow-up audiometry and clinical examination at predetermined intervals (2 weeks, 1, 2, 4, and 6 months, and 1 and 2 years). Propensity score-matching and receiver operating characteristics curves of the initial parameters were used for estimating clinical characteristics. Of the 200 patients, 25 (12.55%) who had abnormal findings suggesting inner ear lesions on MRI were assigned to the secondary SSNHL group; within this group, 10 patients (10/200, 5%) had a tumor invading the IAC, 7 (7/200, 3.5%) had ILH, 6 (6/200, 3%) had labyrinthitis, and 2 (1%) had a structural deformity of the IAC. The secondary group showed significantly poor recovery of hearing function compared with that in the idiopathic group. Patients with ILH or labyrinthitis showed prognoses that were equally poor as those of patients with tumors in the secondary group. Additionally, patients with such lesions showed significant canal paresis on the lesion side at an early stage and a high prevalence of benign paroxysmal positional vertigo (BPPV). In conclusion, the prevalence of non-tumorous lesions on MRI represents common findings and showed a poorer treatment response than that of vestibular Schwannoma in patients with SSNHL. Abnormal canal paresis (cut-off value of 35% on the lesioned side, sensitivity 65.2% and specificity 67%), spontaneous nystagmus directed to the contralesional side, and positional vertigo would be the clinical presentation of SSNHL with IAC lesions, in which the presence of acute prolonged vertigo or positional vertigo compatible with BPPV suggests the possibility of a non-tumorous lesion, such as ILH or a labyrinthitis rather than an IAC tumor.

Dataset Information

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.

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.

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