Immunity After Cochlear Implantation and Perilymph Molecular Profiles in Sensorineural Hearing Loss

With the progress of technologies and surgical methods, cochlear implantation, initially proposed only to patients with completely non-functional inner ear, can be now performed on individuals with still some measurable hearing left in some frequencies. Such patients can additionally benefit from a special treatment by electric-acoustic stimulation (EAS). Combining the electric stimulation with cochlear implant (CI) and acoustic amplification of residual hearing using a conventional hearing aid (HA) can drastically improve one's quality of life and ameliorate the performance in noisy environment as well as music perception.

Since the main condition for EAS is the residual hearing preservation, it is important to understand the reasons of its loss post-cochlear implantation. This loss can occur in 2 periods:

• Early after surgery (˂ 1 month): mainly due to the trauma from electrode insertion. This risk decreases with the development of surgical techniques. Another possible reason is early inflammation processes in the cochleae.
• Later after surgery (˃ 1 month): occurs mainly about 3 months post-implantation in 30-40 % of patients. This loss is the main reason for dropping out the EAS leaving the patient to rely on CI only.

Animal studies suggest that the delayed residual hearing loss might happen as consequence of cochlear fibrosis development, supposedly due to the inflammation and foreign body response to the CI materials within the cochlea. In its natural state, the cochlea does not contain any immune cells and is well protected from immune stimulation by infectious agents. Cochlear implantation, however, provides a single clinical cause for infectious or autoimmune fibrosis. Such immune response might be provoked by autoantigens against cochlear proteins like Cochline or TectB. This study aims to search blood markers of immunisation against inner ear proteins after cochlear implantation. Another goal is to seek potential biomarkers of delayed residual hearing loss directly in perilymph. Proteomic analysis will be performed using Liquid Chromatography - High Resolution Mass Spectroscopy (HRMS) technique.

The main objective of this study is

• to identify, in the perilymph of implanted patients, biomarkers predictive of the delayed residual hearing loss
• to identify blood biomarkers predictive of delayed residual hearing loss in implanted patients

The secondary objectives are

• to describe qualitatively and quantitatively the time evolution for blood biomarkers of interest after cochlear implantation
• to correlate quantitative values of identified biomarkers with clinical data of implanted patients
• to identify perilymph and blood biomarkers of early residual hearing loss post-cochlear implantation
• depending on molecular profiles identified, to study metabolic pathways and mechanisms involved in delayed residual hearing loss post-cochlear implantation
• to seek for blood indicators in favour of anti-cochlear immunisation through screening for peripheral blood mononuclear cells (PBMC)
• to create a bio collection of human perilymph and blood serum biobank of cochlear implants users for future proteomics/molecular studies

Inclusion criteria

for the "Cochlear implantation" group :

• Patients aged 18 years or more
• Indication for the cochlear implantation surgery according to the criteria of French National Authority for Health (Severe to profound sensorineural deafness with indication for cochlear implant surgery: Intelligibility less than or equal to 50% when performing vocal audiometry tests with Fournier's list in free field with recent devices.)
• Presence of "useful" residual hearing ≤ 80 dB on at least 2 consecutive frequencies (in air conduction) from the range 125, 250, 500, 1000 kHz on pure-tone audiometry
• Patients given their free and informed written consent
• Patients affiliated to a French social security system

Inclusion criteria

for the "Control" group:

• Patients aged 18 years or more
• Indication for otological surgery of the middle ear (excluding active infectious or inflammatory pathology e.g. myringoplasty, ossiculoplasty, cure for otosclerosis)
• Normal hearing (non affected inner ear): average hearing loss (mean threshold for the frequencies 500, 1000, 2000, 4000 Hz) ≤ 35 dB in bone conduction
• Patients given their free and informed written consent
• Patients affiliated to a French social security system

Exclusion criteria

for the "Cochlear implantation" group:

• Contraindication to surgery detected during the preoperative assessment
• Pre-implantation cochlear assessment unfavorable to the implantation surgery
• Absence of residual hearing shown by preoperative audiometry
• History of bacterial labyrinthitis or bacterial meningitis
• Cochlear ossification shown on preoperative imaging
• Homozygous pathogenic mutations identified by molecular diagnosis of the SCL26A5 (prestin), TECTB (Beta-Tectorin) genes, and heterozygous of the COCH gene (Cochlin) prior to implantation (if available)
• Vulnerable subject: minors, protected adults as defined by the Public Health Code, pregnant or breastfeeding women, subject under guardianship or subject deprived of liberty
• Participation in another pharmacological therapeutic interventional clinical research

Exclusion criteria

for the Control group:

• Contraindication to surgery detected during the preoperative assessment
• Fluctuating hearing = fluctuating hearing thresholds on at least one ear (shown by past bone conduction pure-tone audiometries)
• History of bacterial labyrinthitis or bacterial meningitis
• Middle ear infection or inflammation on the day of the surgery
• Chronical immune or inflammatory disease
• Active viral or bacterial infection on the day of inclusion visit or surgery
• Fever on the day of the first blood sample
• Vulnerable subject: minors, protected adults as defined by the Public Health Code, pregnant or breastfeeding women, subject under guardianship or subject deprived of liberty
• Participation in another pharmacological therapeutic interventional clinical research