Altered Expression of Autoimmune Regulator in Infant Down Syndrome Thymus, a Possible Contributor to an Autoimmune Phenotype

摘要: Down syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency infections and autoimmune diseases. Patients DS share clinical features, manifestations specific autoantibodies, patients affected polyendocrine type 1. Autoimmune 1 mutations in the regulator (AIRE) gene, located on which regulates expression tissue-restricted Ags (TRAs) thymic epithelial cells. We investigated AIRE TRAs control tissue using quantitative PCR. mRNA levels were elevated from patients, trends toward AIRE-controlled genes INSULIN CHRNA1 found. Immunohistochemical stainings showed altered cell composition architecture medulla individuals frequencies AIRE-positive medullary cells CD11c-positive dendritic well enlarged Hassall's corpuscles. In addition, we evaluated proteomic profile exosomes controls. carried a broader protein pool also larger unique compared exosomes. conclusion, gene dose could contribute to an phenotype through multiple AIRE-mediated effects homeostasis function that affect selection processes.