霉酚酸酯诱导治疗对狼疮性肾炎患者Treg/Th17的影响

The Effect of Mycophenolate Mofetil Induction Therapy on Treg/Th17 in Patients with Lupus Nephritis

目的探讨霉酚酸酯(MMF)对狼疮性肾炎(LN)患者调节性细胞(Treg)/辅助性T细胞17(Th17)的影响。方法纳入2017年1月至2020年4月75例成年系统性红斑狼疮(SLE)患者作为研究对象,SLE活动度评分(SLEDAI)>4分,分为LN组(n=35)和SLE组(n=40)。另外选取同期的30例健康志愿者作为对照组。LN组患者接受6个月MMF诱导治疗,分别采用流式细胞术和酶联免疫吸附测定法检测各组受试者以及LN患者基线、治疗3个月、6个月时外周血Th17、Treg百分比和血清白细胞介素(IL)-17、转化生长因子-beta(TGF-β)水平。结果LN组患者Treg/Th17比值低于对照组和SLE组,同时血清IL-17水平高于对照组和SLE组(P<0.05)。与基线比较,LN患者治疗期间Treg/Th17比值逐渐上升,同时血清IL-17水平和SLEDAI评分逐渐降低(P<0.05),与治疗3个月相比,治疗6个月时LN患者Treg/Th17比值进一步增加,同时血清IL-17水平和SLEDAI评分进一步降低(P<0.05)。经Spearman法分析,基线、3月、6月Treg/Th17与SLEDAI评分呈负相关(r=-0.724、-0.560、-0.336,P<0.05)。完成6个月随访后,12例LN患者达到了完全缓解(CR),14例部分缓解(PR),9例治疗无反应(NR)。CR组和PR组患者Treg/Th17比值和血清TGF-β水平随着治疗的进行逐渐升高,同时血清IL-17水平逐渐降低,且CR组各指标变化趋势较PR组更明显(P<0.05)。结论活动期LN患者外周血Th17亚群明显增加,且普遍存在Treg/Th17比例失衡情况。而经MMF诱导治疗后,外周血Th17亚群比例以及血清IL-17水平逐渐降低,有助于促进Treg/Th17恢复平衡。

Objective To investigate the effect of mycophenolate mofetil(MMF)on regulatory cells(Treg)/helper T cell 17(Th17)in patients with lupus nephritis(LN).Methods During the period of January,2017 to April,2020,75 adult patients with systemic lupus erythematosus(SLE)were included as research subjects,with SLE activity score(SLEDAI)>4 points,and they were divided into the LN group(n=35)and SLE Group(n=40).In addition,30 healthy volunteers during the same period were selected as the control group.Patients in the LN group received MMF induction therapy for 6 months.Flow cytometry and enzyme-linked immunosorbent assay were conducted to detect the percentages of Th17 and Treg in peripheral blood at baseline,3 months,and 6 months of LN patients in each group,as well as serum interleukin(IL)-17 and transforming growth factor-beta(TGF-β)levels.Results Treg/Th17 ratio of the LN group was lower than that of the control group and SLE group,while serum IL-17 level was higher than that of the control group and SLE group(P<0.05).Compared with baseline,Treg/Th17 ratio of LN patients gradually increased during the treatment,while the serum IL-17 level and SLEDAI score gradually decreased(P<0.05).Compared with 3 months of treatment,Treg/Th17 of LN patients at 6 months of treatment showed a further increased ratio,while the serum IL-17 level and SLEDAI score further decreased(P<0.05).According to Spearman analysis,Treg/Th17 at baseline,March,and June were negatively correlated with SLEDAI scores(r=-0.724,-0.560,-0.336,P<0.05).After completing the 6-month follow-up,12 patients with LN achieved complete remission(CR),14 patients with partial remission(PR),and 9 patients did not respond to treatment(NR).Treg/Th17 ratio and serum TGF-βlevels of patients in the CR and PR groups gradually increased with the progress of treatment,while serum IL-17 level gradually decreased,and the trend of changes in various indicators in the CR group was more obvious than that in the PR group(P<0.05).Conclusion The peripheral blood Th17 subgroup of patients with active LN increases significantly,and Treg/Th17 ratio is generally unbalanced.After MMF induction treatment,the proportion of peripheral blood Th17 subgroups and serum IL-17 levels gradually decreases,which can help to promote the restoration of Treg/Th17 balance.