Diabetes Care：炎症基因表达改变或参与T1DM及其并发症的发生

前期的基因表达芯片研究鉴定了1型糖尿病(T1D)患者和胰岛自身抗体阳性受试者之间一些基因表达有差异。为了验证T1D患者中这些基因表达的变化，以及鉴定糖尿病并发症中表达改变的基因，来自佐治亚州摄政大学医学院生物技术和基因组医学中心的Yulan Jin博士等人进行了一项研究，研究发现，由骨髓细胞分泌的炎症介质涉及T1D及其并发症的发生。研究结果在线发表于2013年5月1日的美国《糖尿病治疗》(Diabetes Care)杂志上。

研究人员采用高通量实时RT-PCR法验证928名T1D患者和922名对照者外周血单核细胞(PBMCs)中的基因表达变化。

结果显示，T1D患者与对照者比较，在所分析的18个基因中，8个基因(S100A8, S100A9, MNDA, SELL, TGFB1, PSMB3, CD74和IL12A)表达升高，3个基因(GNLY, PSMA4和SMAD7)表达降低，提示T1D患者PBMCs中参与炎症、免疫调节、抗原加工和提呈的基因表达显著改变。此外，在T1D及并发症患者的骨髓细胞中，粘附分子SELL和3个炎症基因(S100A8, S100A9, 和 MNDA)表达显著升高(比值比[OR] 1.3-2.6，校正后P值=0.005-10^-8)，特别是那些有神经病变的患者(OR 4.8-7.9，校正后P值<0.005)。

这些研究发现表明，主要由骨髓细胞分泌的炎症介质涉及T1D及其并发症的发生。

The Expression of Inflammatory Genes Is Upregulated in Peripheral Blood of Patients with Type 1 Diabetes.
Abstract
OBJECTIVEOur previous gene expression microarray studies identified a number of genes differentially expressed in patients with type 1 diabetes (T1D) and islet autoantibody-positive subjects. This study was designed to validate these gene expression changes in T1D patients and to identify gene expression changes in diabetes complications.RESEARCH DESIGH AND METHODSWe performed high-throughput real-time RT-PCR to validate gene expression changes in peripheral blood mononuclear cells (PBMCs) from a large sample set of 928 T1D patients and 922 control subjects.RESULTSOf the 18 genes analyzed here, eight genes (S100A8, S100A9, MNDA, SELL, TGFB1, PSMB3, CD74, and IL12A) had higher expression and three genes (GNLY, PSMA4, and SMAD7) had lower expression in T1D patients compared with control subjects, indicating that genes involved in inflammation, immune regulation, and antigen processing and presentation are significantly altered in PBMCs from T1D patients. Furthermore, one adhesion molecule (SELL) and three inflammatory genes mainly expressed by myeloid cells (S100A8, S100A9, and MNDA) were significantly higher in T1D patients with complications (odds ratio [OR] 1.3-2.6, adjusted P value = 0.005-10-8), especially those patients with neuropathy (OR 4.8-7.9, adjusted P value <0.005).CONCLUSIONSThese findings suggest that inflammatory mediators secreted mainly by myeloid cells are implicated in T1D and its complications.