Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Department of Molecular Biology, Institute of Clinical Medicine, University of Oslo, P.O Box 1171, 0318 Oslo, Norway; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1110, 0317 Oslo, Norway.
Mol Immunol. 2014 Jun;59(2):208-16. doi: 10.1016/j.molimm.2014.02.018. Epub 2014 Mar 22.
Autoimmune Addison's Disease (AAD) is an endocrine and immunological disease of uncertain pathogenesis resulting from the immune system's destruction of the hormone producing cells of the adrenal cortex. The underlying molecular mechanisms are largely unknown, but it is commonly accepted that a combination of genetic susceptibility and environmental impact is critical. In the present study, we identified multiple hypomethylated gene promoter regions in patients with isolated AAD using DNA isolated from CD4+ T cells. The identified differentially methylated regions were distributed evenly across the 10.5-kb-promoter regions covered by the array, and a substantial number localized to promoters of genes involved in immune regulation and autoimmunity. This study reveals a hypomethylated status in CD4+ T cells from AAD patients and indicates differential methylation of promoters of key genes involved in immune responses.
自身免疫性肾上腺皮质功能减退症(AAD)是一种内分泌和免疫性疾病,其发病机制尚不确定,是由于免疫系统破坏肾上腺皮质的激素产生细胞所致。其潜在的分子机制在很大程度上尚不清楚,但人们普遍认为,遗传易感性和环境影响的结合是至关重要的。在本研究中,我们使用分离自 CD4+T 细胞的 DNA,在单纯性 AAD 患者中鉴定出多个低甲基化基因启动子区域。鉴定出的差异甲基化区域均匀分布在数组覆盖的 10.5kb 启动子区域内,相当数量的区域定位于参与免疫调节和自身免疫的基因的启动子。这项研究揭示了 AAD 患者 CD4+T 细胞中的低甲基化状态,并表明参与免疫反应的关键基因的启动子存在差异甲基化。