Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

中文翻译：

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系统性红斑狼疮低剂量 IL-2 治疗疗效的预测生物标志物：临床分析


低剂量 IL-2 （Ld-IL2） 在系统性红斑狼疮 （SLE） 治疗中显示出良好的治疗效果。然而，之前的临床试验报告了 SLE 反应指数 4 （SRI-4） 反应率为 65.52%-68%，大约一半的人在第 24 周时未能达到主要终点。我们的研究旨在确定 Ld-IL2 的实际使用情况，并确定其在 SLE 中的有效性的决定因素。我们汇总了 342 例接受序贯 Ld-IL2 治疗的 SLE 患者的数据，其中 314 例持续超过 3 个月，被纳入有效性和预测分析。根据 SRI-4，所有患者被分为反应组 （n = 136） 和非反应组 （n = 178）。还分析了狼疮低疾病活动状态 （LLDAS） 以验证我们的结果。皮疹、下补体 3 （C3） 和肾脏受累（包括尿蛋白、尿潜血和尿管型）成为实现 SRI-4 的重要预测因子。使用变化与基线的比率调整基线值显示，反应者和无反应者之间 CD4 + T 细胞免疫谱存在显着差异。ROC 分析证实，皮疹、肾脏受累、CD4 + T 细胞百分比变化和 C3 在预测 SRI-4 方面表现令人满意，AUC 为 0.933。LLDAS 分析显示，血液学受累和较低的 CLA + Treg 是 LLDAS 达标的有效预测标志物。相反，肾脏受累与实现 LLDAS 没有显着关联。SLE 患者背景治疗的分析显示，MMF 联合 Ld-IL2 更可能达到 SRI-4 反应。这些发现揭示了 SLE 患者 Ld-IL2 治疗效果的预测因子，并为医生合理利用提供了指导。