Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease
Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease
复制标题
DOI：
10.1016/j.cyto.2018.12.024
复制
发表时间：
2019-04-01
期刊：
影响因子：
3.8
通讯作者：
Scarpini, E.
中科院分区：
文献类型：
--
作者：
Galimberti, D.;Fenoglio, C.;Scarpini, E.
骨髓细胞表达触发受体 2 基因 (TREM2) 的纯合突变是 Nasu Hakola 病 (NHD) 的主要原因之一。我们分析了携带 TREM2 Q33X 突变的 NHD 患者与杂合子和野生型个体相比，其 164 种炎症因子的外周血单核细胞 (PBMC) 谱。与非携带者相比，NHD 中与骨形成和血管生成相关的几种分子发生了改变：PBMC 中骨形态发生蛋白 (BMP)-1 mRNA 水平显着增加（增加 2.32 倍；P = 0.01），转化生长因子β（TGFB）3水平也是如此（增加1.51倍；P = 0.02）。相反，CXCL5 和 Pro 血小板碱性蛋白 (PPBP) 强烈下调（分别比非携带者降低 -28.26 倍、-9.85 倍，P = 0.01），以及血小板因子 4 变体 1 (PF4V1；-41.44，P = 0.03)。在评估的其他炎症因子中，白细胞介素 (IL)-15 和肿瘤坏死因子与非携带者相比，NHD 中超家族成员 (TNFSF)4 mRNA 水平下降（分别下降-2.25 和 -3.87 倍，P = 0.01 和 0.001）。在杂合子个体中，除了 IL-15 mRNA 水平下降与 NHD 相同程度外，没有观察到显着差异（比非携带者下降 -2.05 倍，P = 0.002）。 NHD 患者 PBMC 中的一个特征包括 CXCL5、PPBP、PF4V1 mRNA 水平大幅降低，IL-15 和 TNFSF4 轻度降低以及 BMP-1 和 TGFB3 轻度升高。
Homozygous mutations in Triggering Receptor Expressed on Myeloid cells 2 gene (TREM2) are one of the major causes of Nasu Hakola Disease (NHD). We analysed Peripheral Blood Mononuclear Cells (PBMC) profile of 164 inflammatory factors in patients with NHD carrying the TREM2 Q33X mutation as compared with heterozygous and wild type individuals.Several molecules related to bone formation and angiogenesis were altered in NHD compared to non-carriers: Bone Morphogenetic Protein (BMP)-1 mRNA levels were significantly increased in PBMC (2.32 fold-increase; P = 0.01), as were Transforming Growth Factor Beta (TGFB)3 levels (1.51 fold-increase; P = 0.02). Conversely, CXCL5 and Pro Platelet Basic Protein (PPBP) were strongly downregulated (-28.26, -9.85 fold-decrease over non-carriers, respectively, P = 0.01), as well as Platelet Factor 4 Variant 1 (PF4V1; -41.44, P = 0.03).Among other inflammatory factors evaluated, Interleukin (IL)-15 and Tumor Necrosis Factor Superfamily Member (TNFSF)4 mRNA levels were decreased in NHD as compared with non-carriers (-2.25 and -3.87 fold decrease, P = 0.01 and 0.001, respectively).In heterozygous individuals, no significant differences were observed, apart from IL-15 mRNA levels, that were decreased at the same extent as NHD (-2.05 fold-decrease over non-carriers, P = 0.002).We identified a signature in PBMC from patients with NHD consisting of strongly decreased mRNA levels of CXCL5, PPBP, PF4V1, mildly decreased IL-15 and TNFSF4 and mildly increased BMP-1 and TGFB3.