Involvement of T-cell receptor-<tex>$\beta$</tex> alterations in the development of otosclerosis linked to **OTSC2**
Faculty of Medicine and Health Sciences
Faculty of Arts. Linguistics and Literature
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Genes and immunity. - Place of publication unknown
, p. 246-253
University of Antwerp
Otosclerosis is a common form of hearing loss, characterized by disordered bone remodeling in the otic capsule. Within the otosclerotic foci, several immunocompetent cells and immune-modulating factors can be found. Different etiological theories involving the immune system have been suggested. However, a genetic component is clearly present. In large otosclerosis families, seven autosomal-dominant loci have been found, but none of the disease-causing genes has been identified. This study focused on the exploration of the second otosclerosis locus on chromosome 7q34-36 (OTSC2), holding the T-cell receptor beta locus (TRB locus). A significantly lower T-cell receptor-β (TCR-β) mRNA expression and percentage of blood circulating TCR-αβ+ T cells was detected in OTSC2 patients compared with controls and patients with the complex form of the disease. Further analysis illustrated more significant disturbances in specific T-cell subsets, including an increased CD28null cell population, suggesting a disturbed T-cell development and ageing in OTSC2 patients. These disturbances could be associated with otosclerotic bone remodeling, given the known effects of immunocompetent cells on bone physiology. These data implicate the TRB locus as the causative gene in the OTSC2 region and represent an important finding in the elucidation of the disease pathology.