Low-dose interleukin-2 as a regulatory immunotherapy for systemic lupus erythematosus

2016 ◽  
Vol 1 ◽  
pp. 15-15
Author(s):  
Masayuki Mizui ◽  
George C. Tsokos
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Interleukin 2 ◽  
Systemic Lupus

scholarly journals Expansion of regulatory T cells using low-dose interleukin-2 attenuates hypertension in an experimental model of systemic lupus erythematosus

2019 ◽  
Vol 317 (5) ◽  
pp. F1274-F1284 ◽  
Author(s):  
Erin B. Taylor ◽  
Jennifer M. Sasser ◽  
Kenji J. Maeda ◽  
Michael J. Ryan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Low Dose ◽  
Interleukin 2 ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
And Control

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that is characterized by prevalent hypertension, renal injury, and cardiovascular disease. Numerous studies have reported a low prevalence and/or impaired function of regulatory T (TREG) cells in both patients with SLE and murine models of the disease. Evidence suggests that TREG cell dysfunction in SLE results from a deficiency in IL-2. Recent studies have reported that low-dose IL-2 therapy expands TREG cells in mouse models of SLE, but whether expanding TREG cells protects against hypertension and renal injury during SLE is unclear. To examine this question, female SLE (NZBWF1) and control (NZW) mice were injected with vehicle or recombinant mouse IL-2 three times in 24 h followed by single maintenance doses every 5 days for 4 wk. Treatment with IL-2 effectively expanded TREG cell populations in the peripheral blood, spleen, and kidneys. Circulating levels of anti-dsDNA IgG autoantibodies, a marker of SLE disease activity, were higher in SLE mice compared with control mice but were unaffected by IL-2 treatment. As previously reported by our laboratory, mean arterial pressure, measured in conscious mice by a carotid catheter, was higher in SLE mice than in control mice. Mean arterial pressure was significantly lower in IL-2-treated SLE mice compared with vehicle-treated SLE mice, suggesting that expanding TREG cells using low-dose IL-2 attenuates the development of hypertension. While the mechanism for the protection against hypertension is unclear, it does not appear to be related to the delay of SLE disease progression.

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

2016 ◽  
Vol 22 (9) ◽  
pp. 991-993 ◽  
Author(s):  
Jing He ◽  
Xia Zhang ◽  
Yunbo Wei ◽  
Xiaolin Sun ◽  
Yaping Chen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Systemic Lupus

Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial

2019 ◽  
Vol 1 (1) ◽  
pp. e44-e54 ◽  
Author(s):  
Jens Y Humrich ◽  
Caroline von Spee-Mayer ◽  
Elise Siegert ◽  
Martina Bertolo ◽  
Angelika Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trial ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Systemic Lupus ◽  
Single Centre

Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus

2015 ◽  
Vol 75 (7) ◽  
pp. 1407-1415 ◽  
Author(s):  
Caroline von Spee-Mayer ◽  
Elise Siegert ◽  
Dimas Abdirama ◽  
Angelika Rose ◽  
Anika Klaus ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Regulatory T Cell ◽  
Low Dose ◽  
Interleukin 2 ◽  
Systemic Lupus

scholarly journals Therapeutic Responses and Predictors of Low-Dose Interleukin-2 in Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Miao Miao ◽  
Yimin Li ◽  
Dan Xu ◽  
Ruijun Zhang ◽  
Jing He ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Skin Rash ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Poor Response ◽  
Systemic Lupus ◽  
Patient Response ◽  
Registration Number

Abstract Objective. Interleukin-2 (IL-2) is effective and well tolerated in patients with systemic lupus erythematosus (SLE). However, patient response to IL-2 therapy varies. Therefore, biomarkers are needed to efficiently identify patients who may respond well to IL-2 treatment. We investigated clinical and immunological biomarkers to predict low-dose IL-2 responses.Methods. A pooled post-hoc analysis was performed in SLE patients who received low-dose IL-2 treatment in two clinical trials. Factors predicting responses in clinical and T-cell subset changes were evaluated by logistic regression. Good response (GR) and poor response (PR) were defined according to whether patients achieved or did not achieve an SLE Responder Index-4 (SRI-4), respectively.Results. A good response at 68% of patients was achieved in the lower Treg group, compared to 0% in the higher Treg group. A good response at 68% was achieved in patients with lower Treg, compared to 0% in patients with higher Treg. In comparison to PR, GR was more strongly associated with low Treg proportions at baseline (12.85±6.07% vs. 9.43±2.82%, P<0.01). There were more patients with skin rash in the GR group than in the PR group (68.75% vs. 30.77%, P=0.042). Multivariate analysis showed that low Treg proportions and skin rash presence were both independently associated with GR to low-dose IL-2 treatment. A nomogram to identify GR probability exhibited a clear discrimination (concordance index, 0.812; 95% confidence interval, 0.64-0.97). Based on the area under the receiver operating characteristic (ROC) curve (AUC) of 0.813, the specificity of a low regulatory T cells (Tregs) proportion (≤13.35%) plus skin rash to predict GR to IL-2 therapy was 100%, with a sensitivity of 68.75%.Conclusion. A low Treg proportion and skin rash indicate GR to low-dose IL-2 treatment in SLE patients.Trial registration number ClinicalTrials.gov Registries ((NCT02465580 and NCT02084238).

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