Department of Rheumatology and Immunology, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Peking University People's Hospital, 11 Xizhimen South St., Beijing, 100044, China.
Clin Rheumatol. 2024 Dec;43(12):3789-3798. doi: 10.1007/s10067-024-07165-2. Epub 2024 Oct 31.
Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS).
A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites.
Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p < 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve.
These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation.
ClinicalTrials.gov number, NCT02464319. Key Points • Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. • Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. • Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients.
低剂量白细胞介素 2（Ld-IL2）作为一种免疫调节治疗方法，越来越多地被用于治疗主要影响 T 细胞亚群的自身免疫性疾病。本研究旨在探讨 Ld-IL2 治疗原发性干燥综合征（pSS）患者的代谢效应。
共招募 60 例患者进行双盲、随机临床试验。其中 50%（30/60）患者接受 Ld-IL2 治疗联合标准治疗 12 周，随后进行 12 周随访。采用干燥综合征反应评估工具（STAR）评估疗效。进行非靶向代谢组学分析以描绘亲水性代谢物谱。
治疗后代谢谱发生显著变化，特别是乙酰辅酶 A、抗坏血酸和谷胱甘肽等代谢物水平升高，这对管理自身免疫性疾病有益。此外，代谢物积累水平与免疫细胞亚群的变化相关（p<0.05），特别是 Tregs。此外，具有特定代谢谱的患者，包括血清中异亮氨酸、ADP、胸苷 5'-三磷酸和其他代谢物水平降低的患者，其反应率较高（91.7%-98.6%），ROC 曲线也证实了这一点。
这些发现表明 Ld-IL2 治疗影响 pSS 的代谢途径，为 Ld-IL2 治疗的系统效应提供了免疫调节以外的深入了解。
ClinicalTrials.gov 编号，NCT02464319。
pSS 中的代谢改变与 Ld-IL2 治疗显著相关。
代谢变化与免疫细胞亚群的变化相关，特别是 Tregs。
代谢组学可能是指导 pSS 患者选择 Ld-IL2 治疗的有用工具。
