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This study aims at defining the role of O-GlcNAcylation is in the physiopathology of systemic lupus erythematosus (SLE). O-GlcNAcylation is a metabolic pathway potentially implicated in SLE with potential for the discovery of new therapeutic strategies.
Systemic lupus erythematosus (SLE) is a rare and potentially life-threatening auto-immune systemic disease. There is an urgent need for better comprehension of the physiopathology of the disease and to discover new therapeutic pathways.
The hexosamine biosynthesis pathway, or HBP, is an important regulator of immunity and results in a post-transductional modification of proteins called O-GlcNAcylation and involved in inflammation and immunity.
There is a very unbalanced sex ratio in favor of women in SLE suggesting a role of the X chromosome in the physiopathology of the disease. The human OGT gene (a key O-GlcNAcylation enzyme) is localized on the X chromosome, near the XIST gene responsible for the inactivation of one X chromosome by methylation.
Moreover, genes encoding CD40L, CXCR3 and OGT have been shown to be demethylated and overexpressed in T cells of women with systemic systemic lupus erythematosus compared to men with the same pathology.
The investigators hypothesize that O-GlcNAcylation is increased in the effector lymphocytes of SLE patients and involved in the pathophysiology of the disease. Therefore, inhibiting O-GlcNAcylation may be a promising therapeutic option in SLE.
This study will recruit 100 patients with SLE followed in Bordeaux University Hospital. Among classical disease activity information, blood samples will be collected at study visit to study O-GlcNAcylation levels in immune cells. Fundamental research will be realized on patients' sample.
Clinical and biological disease activity, treatment and outcomes will be studied in correlation with O-GlcNAcylation levels. Patients will be included within their usual follow-up. No extra visit will be needed and blood samples will be drawn at the same times as those drawn for clinical purposes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Systemic lupus erythematosus (SLE) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sample | Biological | 30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of O-GlcNAcylation level in the blood samples of SLE | At baseline (Day 0) |
| Measure | Description | Time Frame |
|---|---|---|
| Disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) | score (Min value: 0 - Max value: 105), with higher values mean higher disease activity. | At baseline (Day 0) |
| Disease activity according to British Lupus Assessment Group Index 2004 (BILAG-2004) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick BLANCO, Prof | University Hospital, Bordeaux | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux - Service d'Immunologie et Immunogénétique | Bordeaux | France |
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| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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(Min value : 0 - Max value : 4), with higher values mean more severe symptoms |
| At baseline (Day 0) |
| Quantification of OGT biallelic expression in the blood samples of SLE | At baseline (Day 0) |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |