Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study.
Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study.
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DOI：
10.1186/s13075-021-02535-6
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发表时间：
2021-06-11
影响因子：
4.9
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Miao M;Xiao X;Tian J;Zhufeng Y;Feng R;Zhang R;Chen J;Zhang X;Huang B;Jin Y;Sun X;He J;Li Z
采用随机、双盲、安慰剂对照的临床试验研究小剂量IL-2对系统性红斑狼疮（SLE）患者T滤泡调节细胞（Tfr）和T滤泡细胞（Tfh）亚型的调节作用。在接受低剂量IL-2治疗（n=30）或安慰剂（n = 30）以及沿着标准护理治疗的SLE患者（n = 60）的随机队列中进行事后分析。主要终点是在试验第12周达到SLE应答指数-4（SRI-4）。23名健康对照在试验的同时入组进行T细胞亚群检测。基于免疫细胞流式细胞术标记物进行CD 4 T细胞亚群的t-随机近邻嵌入（tSNE）分析，以区分Tfh、Tfh 1、Tfh 2、Tfh 17和Tfr细胞亚群。与HC相比，SLE患者Tfr（CXCR 5 +PD-1 lowTreg和CXCR 5 +PD-1highTreg）细胞的频率显著降低，而促炎Tfh细胞增加。Tfh细胞失衡与多种致病因素（抗dsDNA抗体（r=0.309，P=0.027）和血清IL-17（r=0.328，P=0.021））及SLE疾病活动指数（SLEDAI）评分（r=0.273，P=0.052）相关。CXCR 5 +PD-1 low Treg/Tfh和CXCR 5 +PD-1 low Treg/Tfh 17降低均与免疫球蛋白M（IgM）升高相关（分别为r=-0.448，P=0.002和r=-0.336，P=0.024）。低剂量IL-2治疗的疗效与Tfr/Tfh细胞平衡的恢复相关。这些数据支持这一假设，即促进Tfr与降低疾病活动性和低剂量IL-2治疗可以恢复Tfr/Tfh免疫平衡。ClinicalTrials.gov注册表（NCT 02465580）。在线版本包含补充材料，可通过10.1186/s13075-021-02535-6获得。
To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial. A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets. Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance. These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance. ClinicalTrials.gov Registries (NCT02465580). The online version contains supplementary material available at 10.1186/s13075-021-02535-6.
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影响因子：
7.3
作者：
Qin L;Waseem TC;Sahoo A;Bieerkehazhi S;Zhou H;Galkina EV;Nurieva R
通讯作者：
Nurieva R
循环滤泡 T 辅助细胞与滤泡 T 调节细胞的比率与系统性红斑狼疮的疾病活动度相关
DOI：
10.1016/j.clim.2017.07.004
发表时间：
2017-10
期刊：
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影响因子：
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作者：
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