Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.

Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls.

Association of an SNP with intrathymic transcription of TSHR and Graves' disease: a role for defective thymic tolerance.

Graves' disease (GD) is the paradigm of an anti-receptor autoimmune disease, with agonistic auto-antibodies against the thyrotropin receptor (TSHR-thyroid-stimulating hormone receptor) being the underlying pathogenic effector mechanism. The TSHR belongs to the category of tissue-restricted antigens, which are promiscuously expressed in the thymus and thereby induce central T cell tolerance. In order to understand the association between TSHR gene polymorphisms and GD, we tested the hypothesis that TSHR gene variants affect susceptibility to GD by influencing levels of TSHR transcription in the thymus.