Department of Biochemistry, Basic Medical Sciences Block, Punjab University, Chandigarh, 160014, India,
Rheumatol Int. 2013 Nov;33(11):2819-26. doi: 10.1007/s00296-013-2812-2. Epub 2013 Jul 6.
Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by the production of autoantibodies against a spectrum of nuclear antigens. RANTES and its receptor CCR5 have been associated with the pathogenesis of SLE. The objective of this study is to analyze autoantibodies (DNA/RNA), allelic distribution of RANTES and the association of levels of RANTES and its receptor CCR5 in SLE patients in North Indian region. The RANTES-403 and RANTES-28 polymorphism in the promoter region of RANTES gene was studied in 80 patients and 80 healthy controls. The levels of chemokine RANTES, its receptor CCR5, anti-dsDNA, and anti-SSA antibodies levels were determined. Disease activity was assessed with the systemic lupus erythematosus disease activity index (SLEDAI) score. All the parameters were studied for statistical analysis by using t test (graph pad prism) and correlation by SPSS data. PCR-RFLP performed showed 28C/C and the 403G/G genotypes in both patients and controls, but no other genotypes such as 28C/G, 28G/G and 403A/G, 403A/A were found. Patients had higher levels of RANTES (1840.48 ± 739.42 vs. 835.44 ± 70.48 pg/ml; P < 0.0001) and its receptor CCR5 expression (26.49 ± 0.16 vs. 24.72 ± 3.02 %; P < 0.05) compared to controls. The levels of autoantibodies anti-dsDNA and anti-SSA were also higher in patients than controls. The patients showing elevated anti-dsDNA had negative correlation with SLEDAI score (P < 0.05) while borderline patients were not found to be correlated. In case of anti-Ro/anti-SSA antibody levels, the borderline patients showed a moderately significant negative correlation as compared to controls than patients with elevated autoantibody (P < 0.01). The levels of RANTES and CCR5 were also higher in case of patients than controls. But there was no significant correlation of RANTES and CCR5 with disease activity. We were unable to find an association of RANTES polymorphism with SLE in North Indian population in our sample. No significant difference in allele distribution of RANTES-28 and RANTES-403 in the sample of 160 individuals was detected. Of the two autoantibodies studied, anti-Ro/anti-SSA levels in borderline lupus patients appeared as an important parameter for monitoring/diagnosis of lupus patients.
系统性红斑狼疮(SLE)是一种慢性且复杂的自身免疫性疾病,其特征是产生针对一系列核抗原的自身抗体。RANTES 及其受体 CCR5 与 SLE 的发病机制有关。本研究旨在分析北印度地区 SLE 患者的自身抗体(DNA/RNA)、RANTES 的等位基因分布以及 RANTES 及其受体 CCR5 的水平。在 80 例患者和 80 例健康对照中研究了 RANTES 基因启动子区域的 RANTES-403 和 RANTES-28 多态性。测定趋化因子 RANTES、其受体 CCR5、抗 dsDNA 和抗 SSA 抗体水平。采用系统性红斑狼疮疾病活动指数(SLEDAI)评分评估疾病活动度。使用 t 检验(Graph Pad Prism)和 SPSS 数据进行相关性分析对所有参数进行统计学分析。PCR-RFLP 显示患者和对照组均存在 28C/C 和 403G/G 基因型,但未发现其他基因型,如 28C/G、28G/G 和 403A/G、403A/A。与对照组相比,患者的 RANTES(1840.48±739.42 对 835.44±70.48 pg/ml;P<0.0001)和其受体 CCR5 表达(26.49±0.16 对 24.72±3.02%;P<0.05)水平更高。与对照组相比,患者的自身抗体抗 dsDNA 和抗 SSA 水平也更高。表现出升高的抗 dsDNA 的患者与 SLEDAI 评分呈负相关(P<0.05),而临界值患者则未发现相关性。在抗 Ro/抗 SSA 抗体水平方面,与对照组相比,临界值患者的相关性略呈负相关,而与升高的自身抗体患者相比,相关性则不显著(P<0.01)。与对照组相比,患者的 RANTES 和 CCR5 水平也更高。但 RANTES 和 CCR5 与疾病活动度无显著相关性。我们未能在我们的样本中发现 RANTES 多态性与北印度人群中 SLE 的关联。在 160 个人的样本中未检测到 RANTES-28 和 RANTES-403 的等位基因分布有显著差异。在所研究的两种自身抗体中,边缘性狼疮患者的抗 Ro/抗 SSA 水平似乎是监测/诊断狼疮患者的一个重要参数。