Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
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+CCR7lowPD1high 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.
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.
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.
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.
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 October 20, 2020.
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