Dexamethasone administered by autologous red blood cells (RBCs) is used in clinical trials and as compassionate therapy to alleviate ataxia telangiectasia (AT) symptoms, providing long-term delivery of low doses of the drug. In the present paper, we report a dexamethasone-induced variation in gene expression that differed between healthy and AT primary fibroblasts simulating patient conditions. Gene expression levels were analysed by a microarray platform. The obtained gene-set data were used for biological pathway analysis by Reactome functional network clustering. Over 3000 probes were differentially modulated by dexamethasone in wild-type (WT) and AT fibroblasts. Consequently, the biological pathways induced by dexamethasone treatment also differed between the two samples. Some of the pathways were the same as those normally altered in AT compared to WT cells. Our results were consistent with earlier studies on HDAC4 and DDIT4 dynamics. The 30-day low dose dexamethasone treatment induced differential gene expression in AT and WT cells, leading to the partial recovery of genes that are usually dysregulated in AT. This is probably due to glucocorticoid receptor diversity in AT, which is likely genetically imprinted in AT, thus accounting for the differential response of AT cells to dexamethasone treatment.

通过自体红细胞（RBC）施用的地塞米松被用于临床试验中，并作为具有同情心的疗法来减轻共济失调毛细血管扩张（AT）症状，从而可长期提供低剂量的药物。在本论文中，我们报告了地塞米松诱导的基因表达变化，该变化在模拟患者状况的健康和AT原发性成纤维细胞之间有所不同。基因表达水平通过微阵列平台分析。通过Reactome功能网络聚类，将获得的基因集数据用于生物途径分析。地塞米松在野生型（WT）和AT成纤维细胞中对3000多个探针进行了差异调节。因此，在两个样品之间，地塞米松处理诱导的生物途径也不同。与WT细胞相比，一些途径与AT中通常改变的那些途径相同。我们的结果与关于HDAC4和DDIT4动力学的早期研究一致。30天的低剂量地塞米松治疗诱导了AT和WT细胞中的差异基因表达，导致部分恢复了通常在AT中失调的基因。这可能是由于AT中的糖皮质激素受体多样性所致，该多样性很可能遗传性地印在了AT中，因此可以解释AT细胞对地塞米松治疗的不同反应。