Adipokine gene expression in peripheral blood of adult and juvenile dermatomyositis patients and their relation to clinical parameters and disease activity measures.

Adipokine gene expression in peripheral blood of adult and juvenile dermatomyositis patients and their relation to clinical parameters and disease activity measures.
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DOI:
10.1186/s12950-015-0075-2
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发表时间:
2015
期刊:
Journal of inflammation (London, England)
影响因子:
--
通讯作者:
Reed AM
Reed AM
中科院分区:
其他
文献类型:
--
作者:
Olazagasti JM;Hein M;Crowson CS;de Padilla CL;Peterson E;Baechler EC;Reed AM

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近年来脂肪因子被认为参与了自身免疫性疾病中免疫和炎症反应的调节。为了研究脂肪因子在新诊断的皮肌炎(DM)成人和儿童患者中的作用,我们分析了外周血和骨骼肌中四种脂肪因子的基因表达:内脂素、瘦素、脂联素和脂联素。在两个时间点(基线和6个月)采集21例成人DM、26例青少年DM、5例非疾病成人对照和6例非疾病儿科对照的外周血单核细胞(PBMC)。在基线时收集5名成人DM患者和5名非疾病成人对照的肌肉活检。同样,在基线时收集7例青少年DM患者和5例非疾病儿童对照的肌肉活检。使用定制的RT 2 Profiler PCR阵列生成瘦素、脂联素、内脂蛋白、内脂素和相关炎性细胞因子、IL-6、TNF- α以及管家基因GAPDH、B2 M和ACTB的基因表达水平。与非疾病对照组相比,新诊断的成人DM患者外周血中内脂素基因表达水平显著升高(P = 0.004),这些水平与基线临床参数相关,如年龄(r = 0.34,P = 0.020)、男性(r =-0.35,P = 0.017)、泼尼松使用(r =-0.42,P = 0.006)和DMARD使用(r = 0.35,P = 0.025)。内脂素基因表达水平的变化与疾病活动性指标的变化之间无显著相关性。而visfatin基因表达在青少年DM患者的肌肉组织中显著上调(P = 0.028),在成人DM患者中仅观察到显著性趋势(P = 0.08)。此外,与非疾病成人和儿童对照组相比,成人和青少年DM患者的肌肉基因表达水平显著升高。此外,还观察到外周血中的DPN基因表达与DM疾病活动(包括全身、肌肉和骨骼外疾病活动)之间存在关联。新诊断的成年DM患者外周血内脂素基因表达和肌内脂素基因表达显著增加。进一步的纵向研究应探索使用内脂素和抵抗素等脂肪因子基因表达水平作为糖尿病新型临床诊断生物标志物的可能性。
Recently adipokines have been implicated in the regulation of immune and inflammatory responses in autoimmune disease. To investigate the role of adipokines in adult and pediatric patients with newly diagnosed dermatomyositis (DM), we analyzed peripheral blood and skeletal muscle gene expression of four adipokines: visfatin, leptin, adiponectin and resistin. Peripheral blood mononuclear cells (PBMCs) were collected for 21 adult DM, 26 juvenile DM, 5 non-disease adult controls, and 6 non-disease pediatric controls at two time points: baseline and 6 months. Muscle biopsies from 5 adult DM patients and 5 non-disease adult controls were collected at baseline. Similarly, muscle biopsies from 7 juvenile DM patients and 5 non-disease pediatric controls were collected at baseline. The gene expression levels of leptin, adiponectin, resistin, visfatin and related inflammatory cytokines, IL-6, TNF- α, and housekeeping genes GAPDH, B2M, and ACTB were generated using a custom RT2 Profiler PCR Array. Visfatin gene expression levels in peripheral blood were significantly higher in newly diagnosed adult DM cases compared to non-disease controls (P = 0.004) and these levels correlated with baseline clinical parameters such as age (r = 0.34, P = 0.020), male sex (r = −0.35, P = 0.017), prednisone use (r = −0.42, P = 0.006), and DMARD use (r = 0.35, P = 0.025). No significant association was found between change in visfatin gene expression levels and change in disease activity measures. While visfatin gene expression was significantly up-regulated in muscle tissue of juvenile DM patients (P = 0.028), in adult DM patients only a trend towards significance was observed (P = 0.08). Also, muscle gene expression levels of resistin were significantly elevated in both adult and juvenile DM patients compared respectively to non-disease adult and pediatric controls. Furthermore, an association between peripheral blood resistin gene expression and DM disease activity, including global, muscle, and extra-skeletal disease activity was also observed. Peripheral blood visfatin gene expression and muscle resistin gene expression are significantly increased in newly diagnosed adult DM patients. Further longitudinal studies should explore the possibility of using gene expression levels of adipokines such as visfatin and resistin as novel clinical diagnostic biomarkers in DM.
干扰素诱导趋化因子转录水平升高与系统性红斑狼疮患者疾病活动和器官损伤的关联。
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