Hôpital Henri Mondor, 1 rue Gustave Eiffel,
Créteil, Île-de-France Region, 94000, France
NCT Number: NCT05544448
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
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Notify Me18 year and older
All sexes
Interventional
Not applicable
Créteil, Île-de-France Region, 94000, France
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
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Inclusion criteria
specific by department:
Inclusion criteria
for Clinical Hematology Department:
Inclusion criteria
for Nephrology and Transplantation department:
Inclusion criteria
for Neurology department:
Inclusion criteria
for Rheumatology Department:
Inclusion criteria
for Internal Medicine-Endocrinology Department:
Inclusion criteria
for Dermatology Department:
Exclusion criteria
Non-inclusion criteria common to all patients:
Non-inclusion criteria specific by department:
Non-inclusion criteria for Clinical Hematology Department:
Non-inclusion criteria for Nephrology and Transplantation Department:
Non-inclusion criteria for Neurology Department:
Non-inclusion criteria for Rheumatology Department:
Non-inclusion criteria for Internal Medicine - Endocrinology Department:
Non-inclusion criteria for Dermatology Department:
At inclusion, a blood sample will be taken for research purpose
Time frame: 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
Assistance Publique - Hôpitaux de Paris
Other
Acronym: MuTreg
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