RESUMO
Autoimmune thyroid disease occurs in some complete DiGeorge anomaly patients after thymus transplantation. This study was designed to assess the effect of culture of thymus tissue on the expression of genes involved in the development of autoimmunity. The expression of autoimmune regulator (AIRE), thyroglobulin (TG), thyroid peroxidase (TPO), and cytokeratin RNAs was examined in thymocytes and thymus tissue on the day of thymus harvest and after 14 and 21 days of culture. Immunohistochemistry was used to evaluate the cytokeratin expression in the thymus tissue. AIRE, TG, TPO, and cytokeratin mRNAs were found in harvest-day, 14-day and 21-day cultured tissues. Levels of AIRE, TG, and cytokeratin mRNAs were mostly higher after culture compared to expression on the harvest day, likely secondary to thymocyte depletion.
Assuntos
Expressão Gênica , Linfócitos T/metabolismo , Timo/metabolismo , Timo/transplante , Animais , Meios de Cultura/farmacologia , Humanos , Iodeto Peroxidase/genética , Queratinas/genética , Técnicas de Cultura de Órgãos/normas , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Tireoglobulina/genética , Fatores de Transcrição/genética , Proteína AIRERESUMO
BACKGROUND: Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large-vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposition to LAA stroke varies among ethnicities. We sought to identify genetic factors that contribute to LAA stroke in 2 independent samples of Han Chinese individuals. METHODS AND RESULTS: Novel genetic variants that predispose individuals to LAA stroke were identified using a genome-wide association study (GWAS) of 444 individuals with LAA stroke and 1727 controls in a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 319 cases and 1802 controls. We identified 5 single-nucleotide polymorphisms, including rs2415317 (P=3.10×10(-8)), rs934075 (P=4.00×10(-9)), rs944289 (P=3.57×10(-8)), rs2787417 (P=1.76×10(-8)), and rs1952706 (P=2.92×10(-8)), at one novel locus on chromosome 14q13.3 within PTCSC3 (encoding papillary thyroid carcinoma susceptibility candidate 3) that were associated with LAA stroke at genome-wide significance (P<5×10(-8)). CONCLUSIONS: Our data provide strong support for future studies on the role of PTCSC3 in the pathogenesis of LAA stroke and the association between LAA stroke development and thyroid function. In addition, these findings provide insights into the genetic basis of LAA stroke and identify a novel pathway that might be applicable for future therapeutic intervention.