In Vitro Effect Study of Interleukin-2 Muteins on Regulatory T Cells of Patients With Different Autoimmune, Allo-immune or Inflammatory Diseases
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- the percentage of phosphorylated STAT5 in LTresg compared to LTconv after incubation with IL-2 muteins
研究概览
简要总结
Interleukin 2 (IL-2) is a critical cytokine for the survival and function of regulatory T cells (LTreg). This cytokine has a dual role in the immune system. IL-2 stimulates immune responses by acting on the intermediate affinity IL-2R receptor, IL-2Rβγ, expressed by conventional T cells (LTconv) during activation, but also contributes to the inhibition of immune responses via LTreg that express the high affinity receptor IL-2Rαβγ.
This difference in IL-2 receptor affinity for IL-2 has led to the development of low-dose IL-2 therapy to stimulate LTreg and improve control of excessive inflammation in autoimmune (AID), inflammatory or alloimmune diseases Low-dose IL-2 therapy is being studied in several of these diseases such as systemic lupus erythematosus, type 1 diabetes, alopecia, HCV (hepatitis C virus)-induced vasculitis, atopic dermatitis and chronic allo-transplantation-related graft-versus-host disease (GVHD).
Some of these studies have shown an increase in LTreg numbers and an improvement in certain clinical signs.
To improve LTreg targeting in autoimmune diseases, inflammatory diseases or GVHD, mutated IL-2s (muteins) have been developed with selective LTreg agonist properties.
These IL-2 muteins are linked to an Fc fragment to increase their half-life. Two IL-2 variants (IL-2Vs)-Fc preferentially stimulate STAT5 phosphorylation in LTregs compared to conventional FoxP3- (LTconv) CD4+ or CD8+ T cells
详细描述
Hypothesis:
In order to confirm that this differential effect of IL-2 muteins, already established in non-diseased controls, is also observed in patients with autoimmune diseases, inflammatory diseases or GVHD, a pilot in vitro study should be conducted on a small number of patient's blood samples (5 or 10 depending on the pathology).
Objective :
Conduct a multicentre pilot study to confirm the hypothesis that IL-2 muteins preferentially activate the STAT5 pathway in LTreg compared to LTconv in patients with GVHD, acquired bone marrow aplasia, systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, autoimmune thyroiditis, vitiligo, alopecia or atopic dermatitis
Method:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria common to all patients in different departments:
- •Age18 years
- •Affiliated to social security or entitled to
- •Patient who has been informed of the study and has signed a free and informed consent
- •Inclusion criteria specific by department:
- •Inclusion criteria for Clinical Hematology Department:
- •Patient with GVHD following allogeneic hematopoietic stem cell transplantation (HSC)
- •Or with acquired bone marrow suppression
- •Lymphocytosis > 0.5 G/L
- •Inclusion criteria for Nephrology and Transplantation department:
- •- Patient with systemic lupus erythematosus (ACR classification criteria)
- •Inclusion criteria for Neurology department:
- •- Patient with multiple sclerosis (criteria of Mc Donald 2017)
- •Inclusion criteria for Rheumatology Department:
- •- Patient with rheumatoid arthritis (ACR classification criteria)
- •Inclusion criteria for Internal Medicine-Endocrinology Department:
- •- Patient with Basedow disease, Hashimoto's thyroiditis
- •Inclusion criteria for Dermatology Department:
- •- Patient with vitiligo or alopecia areata or atopic dermatitis
排除标准
- •Non-inclusion criteria common to all patients:
- •Patient under guardianship, curatorship or judicial protection
- •Pregnant, parturient or breastfeeding woman
- •Patient deprived of liberty
- •Patient hospitalized without consent
- •Patient admitted to a health or social institution for purposes other than research
- •Minor patient
- •Adult patient unable to express consent
- •Refusal to participate
- •Patient on AME
- •Non-inclusion criteria specific by department:
- •Non-inclusion criteria for Clinical Hematology Department:
- •Ongoing treatment with high doses (>1 mg/kg/d) of systemic corticosteroid therapy
- •Ongoing treatment with JAK inhibitors
- •Non-inclusion criteria for Nephrology and Transplantation Department:
- •Ongoing treatment with doses >10 mg/d Prednisone
- •Ongoing treatment with Cellcept, Endoxan, Imurel, Belimumab, Anti-CD20, Methotrexate
- •Ongoing treatment with JAK inhibitors
- •Non-inclusion criteria for Neurology Department:
- •Treatment with systemic corticosteroid therapy, Fingolimod or Teriflunomide
- •Ongoing treatment with JAK inhibitors
- •Lymphocytosis < 0.5 G/L
- •Non-inclusion criteria for Rheumatology Department:
- •Ongoing treatment with doses >15 mg/d Prednisone
- •Treatment with Rituximab or Tocilizumab
- •Ongoing treatment with JAK inhibitors
- •Lymphocytosis < 0.5 G/L
- •Non-inclusion criteria for Internal Medicine - Endocrinology Department:
- •Ongoing immunosuppressive therapy
- •Ongoing treatment with JAK inhibitors
- •Non-inclusion criteria for Dermatology Department:
- •Ongoing treatment with Methotrexate
- •Ongoing treatment with JAK inhibitors
- •Ongoing treatment with doses >10 mg/d prednisone
结局指标
主要结局
the percentage of phosphorylated STAT5 in LTresg compared to LTconv after incubation with IL-2 muteins
时间窗: At inclusion
The measurement method is based on the quantification of the phosphorylated STAT5 molecule in LTconv and LTreg by flow cytometry after incubating the cells with IL-2 or IL-2 muteins
次要结局
未报告次要终点