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

NCT05544448 | Completed

• 1 other identifier: APHP220507
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

Autoimmune Diseases; Inflammation; Graft vs Host Disease; T-lymphocytes, Regulatory; Interleukin-2

Outcome Measures

Primary Outcomes (1)

• the percentage of phosphorylated STAT5 in LTresg compared to LTconv after incubation with IL-2 muteins

  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

  At inclusion

Interventions

Blood sample taken at a single time point OTHER

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Henri Mondor, 1 rue Gustave Eiffel,

Créteil, Île-de-France Region, 94000, France

Location

MeSH Terms

Conditions

Autoimmune Diseases; Lupus Erythematosus, Systemic; Multiple Sclerosis; Graft vs Host Disease; Arthritis, Rheumatoid; Thyroiditis, Autoimmune; Vitiligo; Alopecia; Dermatitis, Atopic; Inflammation

Condition Hierarchy (Ancestors)

Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Thyroiditis; Thyroid Diseases; Endocrine System Diseases; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Hypotrichosis; Hair Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a multicenter, open-label, non-controlled, non-randomized in vitro study.

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: October 2, 2023
• Primary Completion: June 6, 2024
• Study Completion: June 6, 2024
• Last Updated: February 11, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)