Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus

He, Jing; Zhang, Xia; Wei, Yunbo; Sun, Xiaolin; Chen, Yaping; Deng, Jun; Jin, Yuebo; Gan, Yuzhou; Hu, Xin; Jia, Ru; Xu, Chong; Hou, Zhaohua; Leong, Yew Ann; Zhu, Lei; Feng, Jinhong; An, Yuan; Jia, Yuan; Li, Chun; Xu, Lan; Yue, Hua; Ren, Limin; Li, Ru; Yao, Haihong; Li, Yuhui; Chen, Shi; Zhang, Xuewu; Su, Yin; Guo, Jianping; Shen, Nan; Morand, Eric Francis; Yu, Di; Li, Zhanguo

doi:10.1038/nm.4148

Cited by 449 publications

(417 citation statements)

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“…Less grade II-IV aGVHD (if IL-2 discontinued early) [36] HCV vasculitis 1-3 × 10 6 IU/m 2 /day from days 1 to 5 every 21 days, 4 courses 90% Clinical response [40] Systemic lupus erythematosus 1 × 10 6 IU/m 2 /day every other day for 14 days, 3-6 courses 95% Clinical response [43] Alopecia areata 1-3 × 10 6 IU/m 2 /day from days 1 to 5 every 21 days, 4 courses 80% Clinical response [42] Type1-diabetus 0.3-3 × 10 6 IU/m 2 /day, daily administration for 5 days Selective Treg increase [41] 1 3…”

Section: Resultsmentioning

confidence: 99%

“…Considering the broad clinical relevance of this mechanism, the restoration of normal Treg homeostasis using low-dose IL-2 could be worth considering for the re-induction of tolerance in patients with autoimmunity as well as GVHD. So far, clinical trials for various autoimmune diseases have been performed and promising results were reported in some diseases including systemic lupus erythematosus (SLE) and type-1 diabetes, as shown in Table 1 [40][41][42][43][44]. Ongoing trials are recruiting patients with other autoimmune diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, and so on.…”

Section: Application For Autoimmune Diseasesmentioning

confidence: 99%

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Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives

Matsuoka

2017

Int J Hematol

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CD4 + CD25 + Foxp3 + Treg is a functionally distinct subset of mature T cells with broad suppressive activity and has been shown to play an important role in the establishment of immune tolerance after HSCT. Altered cytokine environment in post-HSCT lymphopenia with a relative functional deficiency of IL-2 could hamper the reconstitution of Treg, leading to refractory GVHD. Based on the theory of low-dose IL-2 in which Treg can be selectively stimulated through the high-affinity IL-2 receptor, clinical studies have been conducted and demonstrated that low-dose IL-2 administration can restore Treg homeostasis and promote the expansion of this subset on the polymorphic processes of Treg reconstitution after HSCT. The new therapeutic indication of IL-2 for immune tolerance has launched in the field of HSCT and is spreading to the other fields including the treatment for autoimmune diseases. To further extend the indication of low-dose IL-2 to more patients with various immunological problems, the optimization of the timing and dosing of IL-2 intervention and the concomitant immune suppressive therapy according to each patient-based assessment are to be desired in the near future. Further prospective studies may facilitate the development of novel therapeutic algorithms for the effective and safe induction of immune tolerance after HSCT.

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Section: Resultsmentioning

confidence: 99%

Section: Application For Autoimmune Diseasesmentioning

confidence: 99%

Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives

Matsuoka

2017

Int J Hematol

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“…We started our study in 2013, with clinical responses as the primary end point and an emphasis on immuno logical responses, including changes in T FH , T H 17 and T reg cells, as secondary end points 9 . For the first time, we demonstrated that low-dose IL-2 therapy could suppress T FH and T H 17 cells in humans 1 . In addition, using a mouse model, we revealed that suppression of T FH and T H 17 cells was as sensitive to low-dose IL-2 as the promotion of T reg cells.…”

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confidence: 90%

“…We thank Dr Jens Y. Humrich and Dr Gabriela Riemekasten for their interest in our study 1 , which they discussed in a News & Views commentary (Humrich, J. Y. & Riemekasten, G. The rise of IL-2 therapy -a novel biologic treatment for SLE.…”

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confidence: 99%

“…This agrees with the results of many studies on human samples showing that FOXP3 is expressed in activated effector CD4 + T cells in addition to T reg cells 13 . Owing to the limitations of the available phenotypical markers used to characterise T reg cells, we also performed a standard suppressive assay showing that low-dose IL-2 treatment in mice and humans promoted the suppressive function of T reg cells 1 .…”

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confidence: 99%

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The rise of IL-2 therapy — a picture beyond Treg cells

2017

Nat Rev Rheumatol

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Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome

Chen

Miao

et al. 2022

JAMA Netw Open

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ImportancePrimary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches.ObjectiveTo investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS.Design, Setting, and ParticipantsA double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People’s Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020.InterventionsPatients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up.Main Outcomes and MeasuresThe primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24.ResultsSixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, −18.33 points; 95% CI, −28.46 to −8.21 points; P = .001; pain: difference, −10.33 points; 95% CI, −19.38 to −1.29 points; P = .03; fatigue: difference, −11.67 points; 95% CI, −20.65 to −2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells.Conclusions and RelevanceIn this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells.Trial RegistrationClinicalTrials.gov Identifier: NCT02464319

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Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus

Cited by 449 publications

References 28 publications

Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives

Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives

The rise of IL-2 therapy — a picture beyond Treg cells

Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome

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