[Autoimmune Regulatory Gene (AIRE) and Development of Autoimmune Thyroiditis in Down Syndrome]

The autoimmune regulator gene (AIRE), located on chromosome 21, plays a central role in the elimination of autoreactive T lymphocytes through negative selection in the thymus. In Down syndrome (DS), or trisomy 21, AIRE overexpression may occur, which has been associated with a higher prevalence of autoimmune diseases, such as autoimmune thyroiditis.

To analyze the genetic variants of the AIRE gene associated with autoimmunity in individuals with DS, as well as the epigenetic and environmental mechanisms that may modulate its expression and/or function.

An in silico analysis of genetic variants and microRNAs regulating AIRE was conducted by reviewing three bioinformatics platforms. Data processing and graphical analysis were performed using Excel and the R programming language, version 4.3.0.

A total of 1,104 AIRE gene variants associated with autoimmune diseases were identified in Ensembl, and 162 pathogenic or likely pathogenic variants were found in ClinVar. Of these, 19.3% show potential functional impact. However, among the microRNAs encoded on chromosome 21, no conclusive evidence of direct negative regulation of AIRE was identified, except for preliminary in vitro reports involving miR-155.

The overexpression of risk alleles, the presence of structural variants, and epigenetic regulation could explain AIRE dysfunction and the increased prevalence of autoimmune thyroiditis in individuals with DS.