Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People's Republic of China.
Xuzhou Children's Hospital, Xuzhou, Jiangsu, 221002, People's Republic of China.
Pediatr Nephrol. 2018 Feb;33(2):269-276. doi: 10.1007/s00467-017-3791-4. Epub 2017 Nov 2.
Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children.
Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA.
Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level.
The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.
糖皮质激素（GC）是治疗儿童原发性肾病综合征（PNS）最有效的药物之一。然而，有些患者对 GC 反应不佳或无反应。我们的研究目的是观察和描述 PNS 患儿外周血淋巴细胞中组蛋白去乙酰化酶-2（HDAC2）表达水平的差异，并比较不同 GC 治疗反应，主要评估 HDAC2 与 PNS 患儿 GC 耐药之间的相关性。
选择 48 例首次 GC 治疗前 PNS 患儿为研究对象，根据 6 周口服泼尼松治疗反应分为激素敏感型肾病综合征（SSNS；n=25）和激素耐药型 NS（SRNS；n=23）。20 名来自医院体检中心的健康儿童作为对照组；在 GC 治疗前和常规治疗后不同时间点采集外周血。采用 RT-PCR、western blot 和酶联免疫吸附试验（ELISA）技术分别分析外周血淋巴细胞中 HDAC2 mRNA、蛋白表达和活性，采用 ELISA 法检测血清白细胞介素-8（IL-8）水平。
GC 治疗前，SRNS 组 HDAC2 表达水平和活性低于 SSNS 组和对照组，GC 治疗后，各组间 HDAC2 表达和活性差异有统计学意义，SRNS 组 HDAC2 表达和活性低于 SSNS 组和对照组。SSNS 组 GC 治疗后 HDAC2 表达和活性高于 GC 治疗前。SRNS 组不同时间点 HDAC2 表达和活性差异有统计学意义，两组间无统计学差异。SRNS 组治疗前后血清 IL-8 水平均明显高于 SSNS 组。GC 治疗前和 6 周常规治疗后 PNS 患儿 HDAC2 与血清 IL-8 水平呈负相关。
GC 作用受 HDAC2 表达和活性的影响，导致 PNS 患儿血清 IL-8 水平降低。HDAC2 似乎是 PNS 患儿 GC 耐药的标志物之一。
