Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Lupus Sci Med. 2024 Feb 13;11(1):e001072. doi: 10.1136/lupus-2023-001072.
The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE.
Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study.
(1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05).
(1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines.
已有小规模临床试验证实西罗莫司治疗严重或难治性系统性红斑狼疮（SLE）的疗效。然而，很少有研究关注轻度或中度 SLE。因此，本研究旨在阐明西罗莫司添加治疗轻度或中度 SLE 患者的临床疗效。
回顾性收集 17 例连续 SLE 患者的数据。在西罗莫司添加治疗前和治疗后 6 个月，收集 SLE 疾病活动指数-2000（SLEDAI-2K）、临床表现、实验室数据和外周 T 淋巴细胞亚群及细胞因子。通过流式细胞术检测 T 细胞亚群，同时通过多指标微珠流式荧光免疫测定法检测细胞因子。本研究还纳入了 20 名年龄和性别匹配的健康对照者。
（1）SLE 患者外周血淋巴细胞、T 细胞、辅助性 T（Th）细胞、调节性 T（Treg）细胞、Th1 细胞、Th2 细胞和 Treg/Th17 比值明显降低，而 Th17 细胞明显升高与健康对照组相比（p<0.05）。（2）西罗莫司添加治疗 6 个月后，SLE 患者的尿蛋白、全血细胞减少、免疫学指标和 SLEDAI-2K 明显优于西罗莫司治疗前（p<0.05）。（3）SLE 患者治疗后外周血淋巴细胞、T 细胞、Th 细胞、Treg 细胞、Th2 细胞和 Treg/Th17 比值明显高于治疗前（p<0.05）。（4）SLE 患者的血浆白细胞介素（IL）-5、IL-6 和 IL-10 水平明显下降，而 IL-4 水平明显升高与治疗前相比（p<0.05）。
（1）SLE 患者存在 T 细胞亚群失衡，尤其是 Treg/Th17 比值降低。（2）西罗莫司添加治疗可改善 SLE 患者的临床受累、血清学异常和疾病活动，且无不良反应。（3）多靶点治疗有利于增强 Treg 细胞数量，纠正 Treg/Th17 失衡和抗炎细胞因子，同时降低炎症细胞因子。
