Department of Immunology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2010 Apr;95(4):1962-71. doi: 10.1210/jc.2009-1455. Epub 2010 Feb 10.
In monocytes of patients with autoimmune diabetes, we recently identified a gene expression fingerprint of two partly overlapping gene clusters, a PDE4B-associated cluster (consisting of 12 core proinflammatory cytokine/compound genes), a FABP5-associated cluster (three core genes), and a set of nine overlapping chemotaxis, adhesion, and cell assembly genes correlating to both PDE4B and FABP5.
Our objective was to study whether a similar monocyte inflammatory fingerprint as found in autoimmune diabetes is present in autoimmune thyroid disease (AITD).
Quantitative PCR was used for analysis of 28 genes in monocytes of 67 AITD patients and 70 healthy controls. The tested 28 genes were the 24 genes previously found abnormally expressed in monocytes of autoimmune diabetes patients plus four extra genes found in whole-genome analysis of monocytes of AITD patients reported here.
Monocytes of 24% of AITD and 50% of latent autoimmune diabetes of adults (LADA) patients shared an inflammatory fingerprint consisting of the set of 24 genes of the PDE4B, FABP5, and overlapping gene sets. This study in addition revealed that FCAR, the gene for the Fcalpha receptor I, and PPBP, the gene for CXCL7, were part of this proinflammatory monocyte fingerprint.
Our study provides an important tool to determine a shared, specific proinflammatory state of monocytes in AITD and LADA patients, enabling further research into the role of such proinflammatory cells in the failure to preserve tolerance in these conditions and of key fingerprint genes involved.
在自身免疫性糖尿病患者的单核细胞中，我们最近确定了两个部分重叠基因簇的基因表达特征，一个与 PDE4B 相关的基因簇（由 12 个核心促炎细胞因子/化合物基因组成），一个与 FABP5 相关的基因簇（三个核心基因），以及一组九个重叠趋化、黏附和细胞组装基因，与 PDE4B 和 FABP5 相关。
我们的目的是研究在自身免疫性甲状腺疾病（AITD）中是否存在与自身免疫性糖尿病中发现的类似单核细胞炎症特征。
使用定量 PCR 分析了 67 名 AITD 患者和 70 名健康对照者单核细胞中的 28 个基因。所测试的 28 个基因是先前在自身免疫性糖尿病患者单核细胞中异常表达的 24 个基因，加上在此报告的 AITD 患者单核细胞全基因组分析中发现的 4 个额外基因。
24%的 AITD 患者和 50%的成人隐匿性自身免疫性糖尿病（LADA）患者的单核细胞共享一个炎症特征指纹，由 PDE4B、FABP5 和重叠基因集的 24 个基因组成。本研究还表明，Fcarl，即 Fcalpha 受体 I 的基因，和 PPBP，即 CXCL7 的基因，是这种促炎单核细胞特征指纹的一部分。
我们的研究为确定 AITD 和 LADA 患者单核细胞中共同存在的特定促炎状态提供了重要工具，使我们能够进一步研究这些条件下促炎细胞在未能维持耐受中的作用，以及涉及的关键特征指纹基因。
