Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Immunol. 2019 Feb 18;10:159. doi: 10.3389/fimmu.2019.00159. eCollection 2019.
Regulatory T cells (Tregs) researches in systemic lupus erythematosus (SLE) have floundered over the years, reports on the numbers and function of Tregs in SLE present quite contradictory results. We therefore conducted a meta-analysis to verify the changes of Tregs in active SLE. We systematically searched PubMed, Embase, and ISI web of knowledge databases for eligible articles. In total, 628 active SLE patients and 601 controls from 18 studies were included. Due to a high degree of heterogeneity, a random effects model was used to assess the mean differences in Treg percentages, absolute numbers, and suppression capacities of Tregs between active SLE and controls. Further, subgroup analysis was performed to identify potential sources of heterogeneity. The pooled percentages of Tregs in active SLE patients were found to be lower than those in controls (-0.864 ± 0.308, = 0.005), with great heterogeneity ( = 95.01). The discrepancy of published results might result from the following differences among studies: gating strategies for Tregs, diagnostic criteria for SLE, and thresholds of SLEDAI chosen to differentiate between active and inactive SLE. In active SLE, Tregs gated based on CD25 alone showed lower pooled frequency than those gated by Foxp3 or CD127. The percentages of Tregs in active SLE was significantly lower than that in controls when the enrolled SLE patients were diagnosed according to the 1997 modified criteria, whereas they were comparable to controls when diagnosed by the 1982 criteria; the higher threshold of SLEDAI score used to define active SLE tended to achieve a lower percentage of Tregs. The pooled absolute numbers of Tregs in active SLE were significantly decreased compared to those in controls (-1.328 ± 0.374, < 0.001), but seemed to be unaffected by gating strategies. Suppression capacities of Tregs from active SLE patients showed no abnormalities based on the limited pooled data. Longitudinal monitoring of active SLE showed a significant decrease in Treg percentage at remission. This study implies that loss of Tregs may play a role in the pathogenesis of active SLE and help clarify contradictory Treg results in SLE.
调节性 T 细胞（Tregs）在系统性红斑狼疮（SLE）中的研究多年来一直陷入困境，关于 SLE 中 Tregs 数量和功能的报道结果截然不同。因此，我们进行了一项荟萃分析，以验证活动期 SLE 中 Tregs 的变化。我们系统地检索了 PubMed、Embase 和 ISI web of knowledge 数据库中的合格文章。共有 18 项研究的 628 名活动期 SLE 患者和 601 名对照者纳入分析。由于异质性很高，采用随机效应模型来评估活动期 SLE 患者与对照组之间 Treg 百分比、绝对数量和抑制能力的均值差异。此外，还进行了亚组分析以确定潜在的异质性来源。结果显示，活动期 SLE 患者的 Treg 百分比低于对照组（-0.864±0.308， =0.005），且存在很大的异质性（ =95.01）。发表结果的差异可能是由于研究之间存在以下差异：Tregs 的门控策略、SLE 的诊断标准以及用于区分活动期和非活动期 SLE 的 SLEDAI 阈值。在活动期 SLE 中，仅基于 CD25 门控的 Treg 显示出的频率比基于 Foxp3 或 CD127 门控的 Treg 更低。当纳入的 SLE 患者根据 1997 年改良标准诊断时，活动期 SLE 患者的 Treg 百分比明显低于对照组，而根据 1982 年标准诊断时则与对照组相当；用于定义活动期 SLE 的更高的 SLEDAI 评分阈值倾向于获得更低的 Treg 百分比。与对照组相比，活动期 SLE 患者的 Treg 绝对数量显著减少（-1.328±0.374， <0.001），但似乎不受门控策略的影响。根据有限的汇总数据，来自活动期 SLE 患者的 Treg 抑制能力似乎没有异常。对活动期 SLE 的纵向监测显示缓解时 Treg 百分比显著下降。这项研究表明，Treg 的缺失可能在活动期 SLE 的发病机制中起作用，并有助于澄清 SLE 中 Treg 结果的矛盾。
