Akkur Murad A, Areeshi Nuha A, Haqawi Ibrahim Y, AlHabji Ahmed A, Altaher Ahmed H, Jawkhab Hanan A, Fageehi Maram M, Moafa Abdulrahman A, Ismael Ahmed I, Al Alhadi Nouf A
Internal Medicine, Prince Mohammed Bin Nasser Hospital, Jazan, SAU.
Internal Medicine, King Fahad Military Medical Complex, Dhahran, SAU.
Cureus. 2025 May 1;17(5):e83323. doi: 10.7759/cureus.83323. eCollection 2025 May.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, including impaired regulatory T cell (Treg) function. Low-dose interleukin-2 (Ld-IL-2) therapy has emerged as a promising approach to selectively expand Tregs and restore immune tolerance in SLE. This systematic review evaluates current evidence on the efficacy and safety of Ld-IL-2 therapy in patients with SLE. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, the Cochrane Library, and the Virtual Health Library for studies published up to April 10, 2025. Eligible studies included randomized controlled trials, cohort studies, and open-label trials that investigated Ld-IL-2 therapy in adult patients with SLE. Data were extracted on study design, patient demographics, intervention details, clinical and immunologic outcomes, adverse events, and predictive biomarkers. Risk of bias was assessed using the Modified Downs and Black checklist. Seven studies met the inclusion criteria, encompassing a total of 517 patients with active SLE. All studies reported significant expansion of Treg populations following Ld-IL-2 treatment. Clinical outcomes consistently showed reductions in disease activity scores, such as SLEDAI and BILAG, with SRI-4 response rates ranging from 43% to 65.5%. Ld-IL-2 therapy was well tolerated, with adverse events primarily limited to mild injection-site reactions and flu-like symptoms. No serious treatment-related infections or concerns about immunogenicity were observed. Several studies identified baseline biomarkers, including low complement C3 levels, elevated PD-1^hi^ Tregs, and reduced CD4+ T cell counts, as predictors of treatment response. Ld-IL-2 therapy appears to be a safe and effective immunomodulatory treatment for patients with SLE, capable of enhancing Treg function and reducing disease activity. While current evidence is encouraging, larger multicenter randomized trials are warranted to establish standardized treatment protocols and validate predictive biomarkers for optimized patient selection.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其特征为免疫失调，包括调节性T细胞（Treg）功能受损。低剂量白细胞介素-2（Ld-IL-2）疗法已成为一种有前景的方法，可选择性地扩增Tregs并恢复SLE患者的免疫耐受。本系统评价评估了Ld-IL-2疗法治疗SLE患者的疗效和安全性的现有证据。通过在PubMed、Scopus、科学网、Cochrane图书馆和虚拟健康图书馆进行全面的文献检索，查找截至2025年4月10日发表的研究。符合条件的研究包括随机对照试验、队列研究和开放标签试验，这些试验对成年SLE患者进行了Ld-IL-2疗法研究。提取了有关研究设计、患者人口统计学、干预细节、临床和免疫学结果、不良事件以及预测生物标志物的数据。使用改良的唐斯和布莱克清单评估偏倚风险。七项研究符合纳入标准，共纳入517例活动性SLE患者。所有研究均报告Ld-IL-2治疗后Treg群体显著扩增。临床结果一致显示疾病活动评分降低，如SLEDAI和BILAG，SRI-4缓解率在43%至65.5%之间。Ld-IL-2疗法耐受性良好，不良事件主要限于轻度注射部位反应和流感样症状。未观察到严重的治疗相关感染或免疫原性问题。几项研究确定了基线生物标志物，包括低补体C3水平、升高的PD-1^hi^ Tregs和降低的CD4+ T细胞计数，作为治疗反应的预测指标。Ld-IL-2疗法似乎是一种安全有效的SLE患者免疫调节治疗方法，能够增强Treg功能并降低疾病活动度。虽然目前的证据令人鼓舞，但仍需要更大规模的多中心随机试验来建立标准化治疗方案并验证预测生物标志物，以优化患者选择。
