Low dose IL-2 therapy restores regulatory T cells in patients with systemic lupus erythematosus in a dose-dependent manner: a phase IIb trial
Low-dose interleukin 2 (Ld-IL2) has shown therapeutic effects in autoimmune diseases, particularly systemic lupus erythematosus (SLE), yet optimal dosage has not been established in clinical trials. In this multicentre, double-blind, phase IIb trial, 152 patients with active SLE were randomised (1:1:1:1) to receive subcutaneous IL2 (0.2, 0.5, or 1.0 million IU) or placebo every other day for 12 weeks, then weekly for another 12 weeks. At week 12, SRI-4 response rates were higher in the IL2 1 M IU (69.7%), 0.5 M IU (64.7%), and 0.2 M IU (42.9%) groups than the placebo control group (23.5%). Notably, these differences persisted until week 24 (P < 0.001). Moreover, achievement of LLDAS increased in a dose-dependent manner. Patients who received 1 M IU also showed significant reductions in PGA scores, anti-dsDNA antibody titres and prednisone dosages. Infection rates were lower in the IL2 groups compared with placebo. Ld-IL2 drove the expansion of regulatory T cells (Tregs) and altered Treg/effector T cell ratios. These findings highlight the dose-dependent efficacy of IL2 with a favourable safety profile. (Clinicaltrials.gov registration number: NCT04077684).
Authors
- Kuanting Wang
- Ruiling Feng (ORCID: https://orcid.org/0000-0003-1465-3259)
- Yan Ding (ORCID: https://orcid.org/0000-0002-9522-1097)
- T H Li
- Guanmin Gao (ORCID: https://orcid.org/0000-0001-7458-8378)
- Tongjun Mao (ORCID: https://orcid.org/0009-0005-2383-3106)
- Z A Li
- Ke Xu (ORCID: https://orcid.org/0009-0004-0512-785X)
- Yucui Li (ORCID: https://orcid.org/0000-0003-2917-2511)
- Wenping Pan (ORCID: https://orcid.org/0000-0001-7221-7629)
- Q Wang
- Dongbin Jiang
- Yueming Cai
- Jing He (ORCID: https://orcid.org/0000-0003-3904-8928)
- Lingyan Lei
- Yifan Wang
- Wenqiang Fan
- Yongfu Wang
- Yuan Jia
- Xiao Gao
- Xiaolin Sun (ORCID: https://orcid.org/0000-0001-9709-1532)
- Rong Mu
- Huifang Guo
- Na Zhang (ORCID: https://orcid.org/0000-0001-9534-0320)
- Wei Wei
- Ruijun Zhang
- Xia Zhang
- Juan He
- Miaomiao Ma
- Hui Wang
Institutions
- Hebei Medical University (CN)
- China Pharmaceutical University (CN)
- Peking University (CN)
- Tianjin Medical University General Hospital (CN)
- Second Hospital of Hebei Medical University (CN)
- Shandong Mental Health Center (CN)
- Peking University People's Hospital (CN)
- Peking University Shenzhen Hospital (CN)
- Peking University Shougang Hospital (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- Peking University Third Hospital (CN)
- Xinxiang Central Hospital (CN)
- Shandong Provincial QianFoShan Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Shanxi Academy of Medical Sciences (CN)
- Center for Life Sciences (CN)
- Baotou Medical College (CN)
- Shandong First Medical University (CN)
- First Affiliated Hospital of Wannan Medical College (CN)
- Henan Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1038/s41467-026-72245-7
- Primary Topic
- Systemic Lupus Erythematosus Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Peking University
- Beijing Nova Program
- Fundamental Research Funds for the Central Universities