Safety and Efficiency of Low-Dose Interleukin-2 Treatment in Systemic Lupus Erythematosus

Jing He¹, Xia Zhang², Yunbo Wei³, Xiaolin Sun⁴, Jianping Guo⁵, Yuebo JIn⁶, Rulin Jia⁶, Lei Zhu⁶, Zhaohua Hou⁷, Yaping Chen⁸, Yuan An⁶, Yuan Jia⁶, Xu Liu⁶, Limin Ren⁶, Ru Li⁶, HUA YE⁹, Shi Chen⁶, Xuewu Zhang¹⁰, Yin Su¹¹, Eric Morand¹², Yu Di¹³ and Zhanguo Li⁶, ¹Peking Univerisity People's Hospital, Beijing, China, ²Department of Rheumatology & immunology, Peking University People's Hospital, Beijing, China, ³Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of Science, Shandong, China, ⁴People's hospital,Peking University, Beijing, China, ⁵Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China, ⁶Peking University People's Hospital, Beijing, China, ⁷Shandong Analysis and Test Center, Beijing, China, ⁸Monash University, Clayton, Austria, ⁹No.11 XIZHIMENG SOUTH STREET,, Peking University People's Hospital, Beijing, China, ¹⁰Rheumatology, Peking University People's Hospital, Beijing, China, ¹¹Department of Rheumatology and Immunology,Clinical Immunology Center, Peking University People's Hospital, Beijing, China, ¹²Medicine, Monash University, Clayton, Australia, ¹³Molecular Immunomodulation Laboratory, Monash University, Clayton, Austria

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: interleukins (IL), systemic lupus erythematosus (SLE) and treatment, T cells, T-Regulatory Cells

Session Information

Date: Tuesday, November 10, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment VI: Novel Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-system involvement, associated with an imbalance between effector and regulatory CD4+ T cells. The development and activation of these T cell subsetsis critically regulated by interleukin-2 (IL-2) which is impaired in SLE patients. Using animal models and human samples, we characterised precursor Tfh cells in blood with a CXCR5⁺CCR7^lowPD1^high phenotype. The increase of the early memory Tfh cells in blood represents the active Tfh cell differentiation and correlates with the disease activities of systemic lupus erythematosus (SLE). We hypothesized that low-doseIL-2 treatment of SLE would result in selective expansion of regulatory CD4+ T (Treg) cells, while suppressing follicular helper T (Tfh) cells and IL-17-producing helper T (Th17) cells. Our study was to assess the safety and efficacy of low-dose IL-2 therapy in active SLE.

Methods:

Forty patients with active SLE were recruited to a prospective open label study; 38 patients completed three cycles of 1 million IU recombinant human IL-2 (rhIL-2), administered subcutaneously every other day for 2 weeks, followed by a 2-week break. Both clinical and immunological responses were assessed. The primary end points were the SLE Responder Index (SRI) and safety at week 12. Secondary end points were the effects of the therapy on Treg, Tfh and Th17 cells.

Results:

An SRI response was seen in 34/38 patients (89.5%) at week 12. Disease activity measured using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) improved significantly, from a median (range) of 11 (8 – 23) to 4 (0 – 12) (p<0.001). At week 12, resolution of clinical activity present at baseline was observed in multiple domains, including rash (20/24 patients), alopecia (13/14), arthritis (10/11), fever (3/3), leukopenia (18/19) and thrombocytopenia (4/4).No severe adverse events were observed. Significant reductions of anti-dsDNAtitres (p<0.001) and proteinuria (p=0.005), and increased levels of C3 (p<0.001) and C4 (p<0.001), were observed at week 12. Immunological analysis revealed that low-dose rhIL-2 administration was associated with selective expansion of Treg cells (p<0.001) and conversely with reductions of Tfh andTh17cells (p=<0.001), but had not effect on Th1 and Th2 cells.

Conclusion:

Low-dose IL-2 was efficient and well tolerated in active SLE. The improvements in disease activity were associated with selective modulation of CD4⁺ T cell subsets.

Disclosure: J. He, None; X. Zhang, None; Y. Wei, None; X. Sun, None; J. Guo, None; Y. JIn, None; R. Jia, None; L. Zhu, None; Z. Hou, None; Y. Chen, None; Y. An, None; Y. Jia, None; X. Liu, None; L. Ren, None; R. Li, None; H. YE, None; S. Chen, None; X. Zhang, None; Y. Su, None; E. Morand, None; Y. Di, None; Z. Li, None.

To cite this abstract in AMA style:

He J, Zhang X, Wei Y, Sun X, Guo J, JIn Y, Jia R, Zhu L, Hou Z, Chen Y, An Y, Jia Y, Liu X, Ren L, Li R, YE H, Chen S, Zhang X, Su Y, Morand E, Di Y, Li Z. Safety and Efficiency of Low-Dose Interleukin-2 Treatment in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/safety-and-efficiency-of-low-dose-interleukin-2-treatment-in-systemic-lupus-erythematosus-2/. Accessed .

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