Laboratory of Immunobiology for Research and Applications to Diagnosis, Banc de Sang i Teixits (Blood and Tissue Bank), 08916 Badalon, Barcelona, Spain.
J Autoimmun. 2011 May;36(3-4):189-200. doi: 10.1016/j.jaut.2011.01.002. Epub 2011 Feb 26.
Graves' disease (GD) is a chronic autoimmune process in the thyroid gland and involves IFN and IFN driven immune activation. Assuming the thyroid gland is the main site stimulating the autoimmune response, we investigated the role of IFNs and other factors in the chronic evolution of GD by comparing the transcriptomic profiles of thyroid glands from short clinical course (SC), long clinical course (LC) cases, and control glands (C). Over 200 differentially expressed genes of the immune system were identified. Results were extensively analyzed bioinformatically and validated by qPCR in 31 glands. The analysis indicated that GD involved a progressive accumulation of changes with clearly distinct profiles in the SC and LC glands. Humoral response, antigen presentation and chemokines & cytokines were overall the most represented gene ontology categories in LC cases. Ingenuity Pathway Analysis pointed to a few inflammatory pathways in SC cases whereas LC cases involved numerous complex pathways, such us "communication between innate and adaptive immune cells" and "autoimmune thyroid signaling". A broad IFN signature consisted of the over-expression of 74 and 84 type I and type II IFN responsive genes respectively (overall 96 out of 211, 45%), but many of these genes can also be directly activated through cytoplasmic viral receptors. For the first time, plasmocytoid dendritic cells were identified in GD thyroid, but surprisingly, the main producers of IFN-alpha were cells with a myeloid cell phenotype. In addition, cells with the phenotype of alternatively activated macrophages were detected in abundance in GD thyroids, confirming data from the transcriptomic analysis. Collectively, these results confirmed the role of IFNs, suggested other natural immunity triggers, identified new cell types in the local disease process, and expanded our knowledge of the processes that may determine the chronicity of GD.
格雷夫斯病（GD）是甲状腺的慢性自身免疫过程，涉及 IFN 和 IFN 驱动的免疫激活。假设甲状腺是刺激自身免疫反应的主要部位，我们通过比较短临床病程（SC）、长临床病程（LC）和对照腺体（C）的甲状腺转录组谱来研究 IFNs 和其他因素在 GD 慢性演变中的作用。鉴定出 200 多个免疫系统差异表达基因。结果通过生物信息学进行了广泛分析，并在 31 个腺体中通过 qPCR 进行了验证。分析表明，GD 涉及逐渐积累的变化，SC 和 LC 腺体的特征明显不同。体液反应、抗原呈递和趋化因子和细胞因子是 LC 病例中总体上最具代表性的基因本体类别。Ingenuity Pathway Analysis 指出 SC 病例中存在一些炎症途径，而 LC 病例则涉及许多复杂途径，如“先天免疫和适应性免疫细胞之间的通讯”和“自身免疫性甲状腺信号转导”。广泛的 IFN 特征包括分别过表达 74 种和 84 种 I 型和 II 型 IFN 反应基因（总体 211 种中的 96 种，45%），但许多这些基因也可以通过细胞质病毒受体直接激活。首次在 GD 甲状腺中鉴定出浆细胞样树突状细胞，但令人惊讶的是，IFN-α的主要产生细胞是具有髓样细胞表型的细胞。此外，在 GD 甲状腺中还检测到大量具有交替激活巨噬细胞表型的细胞，这证实了转录组分析的数据。总之，这些结果证实了 IFNs 的作用，提出了其他天然免疫触发因素，鉴定了局部疾病过程中的新细胞类型，并扩展了我们对可能决定 GD 慢性的过程的认识。
