Hôpital Edouard Herriot, Lyon, France.
Genes Immun. 2010 Apr;11(3):269-78. doi: 10.1038/gene.2009.112. Epub 2010 Jan 21.
Understanding the pathogenesis of type-I diabetes (T1D) is hindered in humans by the long autoimmune process occurring before clinical onset and by the difficulty to study the pancreas directly. Alternatively, exploring body fluids and particularly peripheral blood can provide some insights. Indeed, circulating cells can function as 'sentinels', with subtle changes in gene expression occurring in association with disease. Therefore, we investigated the gene expression profiles of circulating blood cells using Affymetrix microarrays. Whole-blood samples from 20 first-degree relatives of T1D children with autoimmune diabetes-related antibodies, 19 children immediately after the onset of clinical T1D and 20 age- and sex-matched healthy controls were collected in PAXgene tubes. A global gene expression analysis with MDS approach allowed the discrimination of pre-diabetic subjects, diabetic patients and healthy controls. Univariate statistical analysis highlighted 107 distinct genes differently expressed between these three groups. Two major gene expression profiles were characterized, including type-I IFN-regulated genes and genes associated with biosynthesis and oxidative phosphorylation. Our results showed the presence of early functional modifications associated with T1D, which could help to understand the disease and suggest possible avenues for therapeutic interventions.
理解 1 型糖尿病 (T1D) 的发病机制在人类中受到以下因素的阻碍：在临床发病前发生的长程自身免疫过程，以及直接研究胰腺的困难。相反，探索体液，特别是外周血，可以提供一些见解。事实上，循环细胞可以作为“哨兵”，其基因表达的细微变化与疾病相关。因此，我们使用 Affymetrix 微阵列研究了循环血细胞的基因表达谱。在 PAXgene 管中收集了 20 名 T1D 儿童自身免疫性糖尿病相关抗体的一级亲属、19 名临床 T1D 发病后即刻的儿童和 20 名年龄和性别匹配的健康对照者的全血样本。采用 MDS 方法的全基因组表达分析能够区分糖尿病前期患者、糖尿病患者和健康对照者。单变量统计分析突出了这三组之间表达不同的 107 个独特基因。两个主要的基因表达谱被表征，包括 I 型 IFN 调节基因和与生物合成和氧化磷酸化相关的基因。我们的研究结果表明，T1D 存在与早期功能修饰相关的基因，这有助于理解疾病并为治疗干预提供可能的途径。
