外周血辅助性T细胞17调节性T细胞及二者比值在系统性红斑狼疮的研究

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目的探讨Th17细胞和调节性T细胞在系统性红斑狼疮(SLE)、狼疮肾炎(LN)发生和发展中的作用,以期寻找病情评估的无创性新指标。方法选取SLE患者103例及23名健康体检者,其中LN患者40例,新诊断、未治疗的SLE患者42例。SLE患者非活动组(SLEDAI 0~4分)患者16例、轻度活动组(SLEDAI 5~9分)患者29例、中度活动组(SLEDAI 10~14分)患者26例、重度活动组(SLEDAI≥15分)患者32例。用四色分选流式细胞仪检测外周血CD4+IL-17+Th17细胞和CD4+CD25+FOXP3+Treg细胞百分数,分析其与疾病活动性(SLEDAI评分)、补体C3、C4和肾脏受累的关系。结果 1SLE轻度、中度、重度活动组Th17细胞百分数均高于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05);SLE中度、重度活动组Th17细胞均高于SLE轻度活动组,差异均有统计学意义(P<0.05);LN组Th17细胞高于非LN组,差异有统计学意义(P<0.05);新发SLE活动组Th17细胞百分数高于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05)。补体降低组SLE患者Th17细胞高于补体正常组及健康对照组,差异均有统计学意义(P<0.05)。Th17细胞百分数与SLEDAI评分呈正相关。2SLE中度、重度活动组Treg细胞百分数均低于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05);SLE重度活动组Treg细胞低于SLE轻度活动组,差异有统计学意义(P<0.05)。LN组Treg细胞与非LN组差异无统计学意义。新发SLE活动组Treg细胞百分数低于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05)。补体降低组SLE患者Treg细胞低于补体正常组及健康对照组,差异均有统计学意义(P<0.05)。Treg细胞百分数与SLEDAI评分无相关性。3SLE轻度、中度、重度活动组Th17/Treg比值均高于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05);SLE中度、重度活动组Th17/Treg比值均高于SLE轻度活动组,差异均有统计学意义(P<0.05);LN组Th17/Treg高于非LN组,差异有统计学意义(P<0.05)。新发SLE活动组Th17/Treg细胞比值高于健康对照组和SLE非活动组,差异均有统计学意义(P<0.05)。补体降低组SLE患者Th17/Treg比值高于补体正常组及健康对照组,差异均有统计学意义(P<0.05)。Th17/Treg比值与SLEDAI评分呈正相关。结论活动性SLE患者外周血Th17细胞升高、Treg细胞下降,Th17/Treg细胞比值与疾病活动呈正相关,提示SLE发病不仅仅是Th17细胞升高或Treg细胞下降,而是二者相互作用导致免疫失衡导致。 Objective To investigate the role of Th17 cells and regulatory T cells in the pathogenesis and development of systemic lupus erythematosus (SLE) and lupus nephritis (LN) in order to find novel noninvasive indicators for disease assessment. Methods 103 patients with SLE and 23 healthy subjects were selected, including 40 LN patients and 42 newly diagnosed and untreated SLE patients. There were 16 patients in SLE patients with inactive SLEDAI (0 ~ 4), 29 patients in mild active group (SLEDAI 5 ~ 9), 26 patients in moderate active group (SLEDAI 10 ~ 14), 26 patients in severe active group SLEDAI ≥ 15 points) in 32 patients. The percentages of CD4 + IL-17 + Th17 cells and CD4 + CD25 + FOXP3 + Treg cells in peripheral blood were measured by four-color sorting flow cytometry. The correlations between them and disease activity (SLEDAI score), complement C3, C4 and kidney involvement relationship. Results The percentages of Th17 cells in mild, moderate and severe activities of 1SLE group were significantly higher than those in healthy control group and SLE inactive group (P <0.05). Th17 cells in moderate and severe active SLE group were higher than SLE mild activity group, the differences were statistically significant (P <0.05); Th17 cells in LN group was higher than non-LN group, the difference was statistically significant (P <0.05); the percentage of newly diagnosed SLE activity Th17 cells was higher than healthy The difference between the control group and inactive SLE group was statistically significant (P <0.05). The level of Th17 in SLE patients with complement reduction group was higher than that in normal complement control group and healthy control group (P <0.05). Th17 cell percentage was positively correlated with SLEDAI score. The percentage of Treg cells in moderate and severe active group was lower than those in healthy control group and SLE inactive group (P <0.05). The levels of Treg cells in SLE severe active group were lower than those in SLE mild active group Statistical significance (P <0.05). LN group Treg cells and non-LN group, the difference was not statistically significant. The percentage of Treg cells in newly diagnosed SLE patients was lower than that in healthy controls and inactive SLE patients (P <0.05). Treg cells in SLE patients with complement reduction group were lower than those in normal controls and healthy controls (P <0.05). There was no correlation between Treg cell percentage and SLEDAI score. The Th17 / Treg ratio in 3SLE mild, moderate and severe active groups were higher than those in healthy control group and SLE inactive group (P <0.05). Th17 / Treg ratio in moderate and severe active group (P <0.05). The level of Th17 / Treg in LN group was higher than that in non-LN group, the difference was statistically significant (P <0.05). The ratio of Th17 / Treg cells in newly diagnosed SLE patients was significantly higher than that in healthy controls and SLE inactive patients (P <0.05). The Th17 / Treg ratio in patients with complement reduction was significantly higher than that in normal controls and healthy controls (P <0.05). Th17 / Treg ratio was positively correlated with SLEDAI score. Conclusions Th17 cells in peripheral blood of patients with active SLE are increased, Treg cells are decreased and the ratio of Th17 / Treg cells is positively correlated with disease activity, suggesting that the pathogenesis of SLE is not only the increase of Th17 cells or the decrease of Treg cells but the interaction between the two Imbalance caused.
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