Chan Rebecca Wing-Yan, Lai Fernand Mac-Moune, Li Edmund Kwok-Ming, Tam Lai-Shan, Chow Kai-Ming, Li Philip Kam-Tao, Szeto Cheuk-Chun
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, China.
Nephrol Dial Transplant. 2006 Jun;21(6):1534-40. doi: 10.1093/ndt/gfk102. Epub 2006 Jan 31.
Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis. Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response.
Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-gamma) after immunosuppressive treatment, although the change of IFN-gamma was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-gamma (r = 0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-beta (r = 0.51, P = 0.002) and MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-gamma (r = 0.45, P = 0.009), T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-beta (r = 0.44, P = 0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period.
The mRNA expression of T-bet, IL-10, TGF-beta, MCP-1, and probably IFN-gamma in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity.
既往研究表明，活动性狼疮患者尿沉渣中靶基因的信使核糖核酸（mRNA）表达增加。我们研究免疫抑制治疗对活动性狼疮性肾炎患者尿基因表达谱的影响。方法。我们招募了9例患有活动性系统性红斑狼疮（SLE）和肾脏疾病且需要使用皮质类固醇治疗（有或无细胞毒性治疗）的患者。对他们进行了6个月的随访，在0、4、12和24周收集尿样，并通过聚合酶链反应测定基因表达谱。将基因表达模式与治疗反应的临床参数进行比较。
在研究的靶基因中，免疫抑制治疗后，T盒转录因子（T-bet）、白细胞介素（IL）-10、转化生长因子-β（TGF-β）、单核细胞趋化蛋白-1（MCP-1）和干扰素-γ（IFN-γ）的尿表达呈逐渐下降趋势，尽管IFN-γ的变化无统计学意义。它们尿表达的时间进程与系统性红斑狼疮疾病活动指数（SLEDAI）所反映的全身活动情况平行。在整个研究期间，SLEDAI评分与IFN-γ（r = 0.43，P = 0.009）、T-bet（r = 0.40，P = 0.016）、TGF-β（r = 0.51，P = 0.002）和MCP-1（r = 0.38，P = 0.022）的表达显著相关。抗双链（anti-ds）DNA抗体滴度与IFN-γ（r = 0.45，P = 0.009）、T-bet（r = 0.37，P = 0.034）、IL-10（r = 0.59，P<0.001）、TGF-β（r = 0.44，P = 0.010）和MCP-1（r = 0.49，P = 0.004）的表达显著相关。另一方面，在整个研究期间，IL-2、IL-4、IL-12、IL-18和GATA-3的表达水平保持稳定。
成功的免疫抑制治疗可使活动性狼疮性肾炎患者尿沉渣中T-bet、IL-10、TGF-β、MCP-1以及可能的IFN-γ的mRNA表达改善，且基因表达谱的变化与临床疾病活动同步。检测靶基因的尿mRNA表达可能是监测狼疮疾病活动的一种潜在非侵入性工具。
