Olazagasti Jeannette M, Hein Molly, Crowson Cynthia S, de Padilla Consuelo Lopez, Peterson Erik, Baechler Emily C, Reed Ann M
Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN USA.
Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN USA ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN USA.
J Inflamm (Lond). 2015 Apr 9;12:29. doi: 10.1186/s12950-015-0075-2. eCollection 2015.
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 RT(2) 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.
近期研究表明，脂肪因子参与自身免疫性疾病中免疫和炎症反应的调节。为了探究脂肪因子在新诊断的成人和儿童皮肌炎（DM）患者中的作用，我们分析了四种脂肪因子（内脂素、瘦素、脂联素和抵抗素）在外周血和骨骼肌中的基因表达情况。
收集21例成年DM患者、26例幼年DM患者、5例非疾病成年对照者和6例非疾病儿童对照者在两个时间点（基线和6个月）的外周血单个核细胞（PBMC）。在基线时收集5例成年DM患者和5例非疾病成年对照者的肌肉活检样本。同样，在基线时收集7例幼年DM患者和5例非疾病儿童对照者的肌肉活检样本。使用定制的RT(2) Profiler PCR Array检测瘦素、脂联素、抵抗素、内脂素以及相关炎性细胞因子IL-6、TNF-α的基因表达水平，同时检测看家基因GAPDH、B2M和ACTB的表达水平。
与非疾病对照者相比，新诊断的成年DM患者外周血中内脂素基因表达水平显著升高（P = 0.004），且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）、泼尼松使用情况（r = -0.42，P = 0.006）和DMARD使用情况（r = 0.35，P = 0.025）。内脂素基因表达水平的变化与疾病活动度指标的变化之间未发现显著关联。虽然幼年DM患者肌肉组织中内脂素基因表达显著上调（P = 0.028），但在成年DM患者中仅观察到有显著意义的趋势（P = 0.08）。此外，与非疾病成年和儿童对照者相比，成年和幼年DM患者肌肉中抵抗素基因表达水平均显著升高。此外，还观察到外周血抵抗素基因表达与DM疾病活动度之间的关联，包括整体、肌肉和骨骼外疾病活动度。
新诊断的成年DM患者外周血内脂素基因表达和肌肉抵抗素基因表达显著增加。进一步的纵向研究应探索将内脂素和抵抗素等脂肪因子的基因表达水平用作DM新型临床诊断生物标志物的可能性。
