Systemic Lupus Erythematosus
Conditions
Keywords
Systemic lupus erythematosus, ferroptosis, autoimmunity
Brief summary
The study aims at defining the role of ferroptosis s in the physiopathology of systemic lupus erythematosus (SLE). Ferroptosis (phenomenon of cellular death regulated by iron) is a metabolic pathway potentially implicated in SLE with potential for the discovery of new therapeutic strategies.
Detailed description
Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting various organs. Regulatory T cells (Treg) and platelets play a crucial role in the pathogenesis of SLE by regulating immunity and promoting inflammation. Ferroptosis, an iron-regulated cell death process, is emerging as a key player in many diseases, including SLE. The project, FERROLUP, aims to understand the role of ferroptosis in SLE and to explore the therapeutic potential of selenium compounds to modulate this process. Recent work has identified down-regulation of glutathione peroxidase 4 (GPx4) by immune complexes and interferon-alpha in neutrophils, leading to ferroptosis and worsening of SLE. In addition, data suggest the involvement of ferroptosis in lupus nephritis. The Bordeaux team has developed selenium compounds, GPx4 mimics, capable of inhibiting ferroptosis in lupus neutrophils. These compounds have shown promising efficacy in mouse models and preliminary human studies in another inflammatory disease. The FERROLUP project aims to characterize the level of lipid peroxidation and GPx4 expression in SLE patients, and to test the impact of selenium compounds on the inhibition of ferroptosis induced by P-selectin, a molecule involved in Treg dysfunction.
Interventions
BIOLOGICALblood sample
30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation
Sponsors
University Hospital, Bordeaux
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age ≥ 18 years; * diagnosis of systemic lupus erythematosus; * being affiliated to health insurance, willing to participate and to sign informed consent; * control group : patients with a diagnosis of rheumatoid arthritis or an inflammatory bowel disease.
Exclusion criteria
* pregnant or breastfeeding women; * patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measurement of lipid peroxidation in regulatory T lymphocytes population in lupus subjects. | At baseline (Day 0) |
Secondary
| Measure | Time frame |
|---|---|
| Measurement of lipid peroxidation in regulatory T lymphocytes population in lupus subjects and controls. | At baseline (Day 0) |
| Measurement of lipid peroxidation in other immune cells (T and B lymphocyte populations) in lupus subjects and controls | At baseline (Day 0) |
| GPX4 expression in lupus subjects and controls. | At baseline (Day 0) |
| Correlation between ferroptosis markers and the level of activity in B lymphocyte populations | At baseline (Day 0) |
| In-vitro effect of BXT on different T lymphocytes population in the presence of P-selectin in sera of lupus subjects and controls | At baseline (Day 0) |
Countries
France
Contacts
CONTACTChristophe RICHEZ, Prof
CONTACTThomas BARNETCHE, PhD
PRINCIPAL_INVESTIGATORChristophe RICHEZ, Prof
University Hospital, Bordeaux
Outcome results
None listed