Antibodies against a 30 Kilodalton Cochlear Protein and Type II and IX Collagens in the Serum of Patients with Inner Ear Diseases

Abstract

Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and LX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens U, LX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot. Anti-type II and anti-type LX antibodies were found in a high percentage of patients with Meniere's disease, otosclerosis, and strial atrophy. Six patients (29%), and all control patients, had no detectable antibodies to these proteins by our assay.

Antibodies against Inner-Ear Proteins in the Sera of Patients with Inner-Ear Diseases

“…In a previous investigation we also found that 3 of 6 patients with Meniere's disease had antibodies directed against a 30-kD protein extracted from human inner ear in Western blotting [8]. Recently, using guinea pig innerear extracts, Cao et al [10] demonstrated that a 30-kD band was detected in sera from patients with various inner-ear diseases, especially in Meniere's disease and PSNHL, in accordance with our study.…”

Molecular markers for cell types of the inner ear and candidate genes for hearing disorders

“…The different collagens might be particularly important for processes that sculpt the elaborate compartments of the inner ear during morphogenesis. This speculation is corroborated by the observation that perturbations of collagen metabolism lead to abnormal aural structure (31) and that autoimmune responses against type II and IX collagens culminate in progressive hearing loss (32,33). Candidate Genes for Hearing Disorders.…”

Idiopathic Sudden Sensorineural Hearing Loss

“…Clinical observations [32] and laboratory findings [33] as well as experimental evidence [34] are presented to support such an exciting hypothesis. However, the immunological theory comes up against the simple fact that the specificity of cochlear antigens against which antibodies have been described [35,36] is highly controversial. This makes it difficult to diagnose auto-immune disease when no systemic manifestations suggest an immune disorder.…”