辅助性T17细胞功能异常在系统性红斑狼疮中的意义

Significance of functional abnormality of T helper 17 cells in systemic lupus erythematosus

目的探讨辅助性T（Th）17细胞介导的炎症损伤与系统性红斑狼疮（SLE）的关系。方法采用酶联免疫吸附试验（ELISA）检测102例SLE患者及68例健康对照血清白介素17A（IL-17A）水平；实时荧光定量聚合酶链反应方法相对定量分析27例SLE患者及13例健康对照外周血单一核细胞（PBMC）中孤核受体γt（RORγt）基因表达水平；分析血清IL-17A水平与RORγt基因表达之间及其分别与SLE疾病活动度（SLEDAI）、SLE是否合并肾脏病变的关系。结果102例SLE患者血清IL-17A水平[14．75（5．12—69．76）ng／L]较68例健康对照组[5．77（2．22～9．60）ng／L]显著升高（P〈0．01）。102例SLE患者血清IL-17A与血清C反应蛋白、血浆肌酐、尿管型呈正相关（分别为r=0．33、P〈0．01，r=O．26、P〈0．05，r=0．27、P〈0．05）；与SLEDAI无显著相关（P〉0．05）。27例SLE患者RORγt基因表达水平较13例健康对照组显著升高[1（0．40～2．62）和0．19（0．15～0．75），P〈0．01]。27例SLE患者RORγt基因表达水平与血清IL-17A水平呈正相关（r=0．47，P〈O．01），与血清补体3之间呈负相关（r=-0．46，P〈0．05）。SLE病情高活动组与低活动组、SLE合并肾脏病变与SLE无合并肾脏病变组间血清IL-17A、RORγt基因表达水平差异均无统计学意义（P值均〉0．05）。结论Th17细胞介导的炎症损伤可能参与了SLE的发病，与SLE肾脏病变可能有关，但其可能不是SLE病情活动惟一的影响因素，在SLE及SLE肾脏受累中可能均不是主导因素。

Objective To estimate the relationship between T helper 17 （Thl7） cell-mediated inflammatory damage and systemic lupus erythematosus （SLE）. Methods Serum intedeukin （IL）-17A levels were measured by enzyme-linked immunosorbent assay （ELISA） in 102 patients with SLE and 68 normal human controls. Real time-quantitative PCR was used to quantify the expression levels of RORγt mRNA in peripheral blood mononuelear cells （PBMCs） from 27 patients with SLE and 13 normal human controls. Linear regression analysis and Spearman correlation analysis were conducted to assess the relationship of serum IL-17A levels with RORγt mRNA expression, SLE disease activity index （SLEDAI）, and the concurrence of renal damage. Results There was a significant increase in serum IL-17A levels and RORγt mRNA expression in patients with SLE compared with the normal controls [ 14.75 （5.12 - 69.76） vs. 5.77 （2.22 - 9.60） ng/L, P 〈 0.01; 1（0.40 - 2.62） vs. 0.19 （0.15 - 0.75 ）, P 〈 0.01 ]. The serum levels of IL-17A in patients with SLE were positively correlated with the levels of serum C-reactive protein, plasma ereatinine and prevalence of urinary cast （r = 0.33, P 〈 0.01; r = 0.26, P 〈 0.05; r = 0.27, P 〈 0.05）, but unrelated to SLEDAI （P 〉 0.05）. The mRNA expression level of RORγt was positively correlated with serum IL-17A levels （r = 0.47, P 〈 0.01 ）, but negatively correlated with serum C3 levels in patients with SLE（r = -0.46, P 〈 0.05）. There was no significant difference in the levels of serum IL-17A or RORγt mRNA expression between patients with highly and lowly active SLE or between patients with and without renal damage （all P〉 0.05）. Conclusions Th17 cell-mediated inflammatory damage may be involved in the pathogenesis of SLE, and associated with renal damage, but is unlikely the only factor affecting the activity of SLE or predominant factor in the pathogenesis of SLE and concurrent renal damage.