The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2

Jia, Wei Hua; Zhang, Sheng‐Xiao; Hao, Yu‐Fei; Qiu, Mengting; Luo, Jing; Li, Yu-Yao; Gao, Chong; Li, Xiaofeng

doi:10.1177/2040622320916014

Cited by 36 publications

(25 citation statements)

References 33 publications

(57 reference statements)

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“…Brief reports from open-label, therapy-controlled, single-center studies in patients with primary Sjogren’s syndrome ( 66 ), polymyositis/dermatomyositis ( 67 ) and psoriatic arthritis (uncontrolled) ( 68 ) have been published more recently by the same group. 99, 31 and 22 patients, respectively, were treated with a short-term regimen of low-dose IL-2 therapy consisting of one 5-day cycle with daily injections of 0.5 million IU of IL-2.…”

Section: Pilot Studies and Clinical Trialsmentioning

confidence: 99%

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

et al. 2021

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Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells. In addition, in some autoimmune diseases, a relative deficiency of IL-2 develops during disease pathogenesis leading to a disturbance of Treg homeostasis, which further amplifies the vicious cycle of tolerance breach and chronic inflammation. Low-dose IL-2 therapy aims either to compensate for this IL-2 deficiency to restore a physiological state or to strengthen the Treg population in order to be more effective in counter-regulating inflammation while avoiding global immunosuppression. Here we highlight key findings and summarize recent advances in the clinical translation of low-dose IL-2 therapy for the treatment of autoimmune and rheumatic diseases.

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Section: Pilot Studies and Clinical Trialsmentioning

confidence: 99%

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

et al. 2021

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“…The number of adoptively transferred Tregs was identified to enable a comparison to our earlier studies (21), where the 2x10 5 polyclonal Tregs controlled depigmentation in in the human Tyrosinase TCR Transgenic-HLA-A2 (h3TA2) mouse model between 3-9 weeks old mice. All groups received low dose of recombinant human IL-2 (3,000 IU) 3 times a week throughout the entire experiment to promote in vivo stimulation of adoptively transferred Tregs (45,46). Animals were maintained for 15 weeks and humanely euthanized.…”

Section: Adoptive Treg Transfermentioning

confidence: 99%

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

et al. 2020

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Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo. CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.

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“…CD4 + Tregs play a central role in immune tolerance, and Treg dysfunction is well described in autoimmune disorders. In vivo, Treg expansion through low-dose IL-2 treatment has been reported in a number of diseases, including chronic graft-versus-host disease (cGVHD), type 1 diabetes, SLE and several other autoimmune diseases (AIDs) [1][2][3][4][5][6][7]. These studies indicated that this treatment is well tolerated and effective, but prediction of patients who may have a better response to low-dose IL-2 is still a challenge in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

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

Miao

et al. 2021

Preprint

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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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The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2

Cited by 36 publications

References 33 publications

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

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

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