In Vitro Effect Study of Interleukin-2 Muteins on Regulatory T Cells of Patients With Different Autoimmune, Allo-immune or Inflammatory Diseases

NCT ID: NCT05544448

Last Updated: 2026-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-02
• Study Completion Date: 2024-06-06

Brief Summary

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

Detailed Description

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:

At the inclusion, patients will have a blood sample collected for in vitro research purposes. Their clinical data will also be collected.

Conclusion This trial should provide in vitro proof-of-principle of the efficacy of IL-2 muteins on LTreg and could eventually lead to a therapeutic trial

Conditions

Autoimmune Diseases; Inflammatory Disease; Acquired Bone Marrow Aplasia; Systemic Lupus Erythematosus; Multiple Sclerosis; Gvhd; Rheumatoid Arthritis; Autoimmune Thyroiditis; Vitiligo; Alopecia; Atopic Dermatitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Interventions

Blood sample taken at a single time point

At inclusion, a blood sample will be taken for research purpose

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Patient with GVHD following allogeneic hematopoietic stem cell transplantation (HSC)
• Or with acquired bone marrow suppression
• Lymphocytosis > 0.5 G/L

• Patient with systemic lupus erythematosus (ACR classification criteria)

• Patient with multiple sclerosis (criteria of Mc Donald 2017)

• Patient with rheumatoid arthritis (ACR classification criteria)

• Patient with Basedow disease, Hashimoto's thyroiditis

• Patient with vitiligo or alopecia areata or atopic dermatitis

• 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

• Ongoing treatment with high doses (>1 mg/kg/d) of systemic corticosteroid therapy
• Ongoing treatment with JAK inhibitors

• Ongoing treatment with doses >10 mg/d Prednisone
• Ongoing treatment with Cellcept, Endoxan, Imurel, Belimumab, Anti-CD20, Methotrexate
• Ongoing treatment with JAK inhibitors

• Treatment with systemic corticosteroid therapy, Fingolimod or Teriflunomide
• Ongoing treatment with JAK inhibitors
• Lymphocytosis < 0.5 G/L

• Ongoing treatment with doses >15 mg/d Prednisone
• Treatment with Rituximab or Tocilizumab
• Ongoing treatment with JAK inhibitors
• Lymphocytosis < 0.5 G/L

• Ongoing immunosuppressive therapy
• Ongoing treatment with JAK inhibitors

• Ongoing treatment with Methotrexate
• Ongoing treatment with JAK inhibitors
• Ongoing treatment with doses >10 mg/d prednisone

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Henri Mondor, 1 rue Gustave Eiffel,

Créteil, Île-de-France Region, France

Countries

France

Other Identifiers

APHP220507

Identifier Type: -

Identifier Source: org_study_id