O-GlcNAcylation Role in the Pathophysiology of Systemic Lupus Erythematosus

University Hospital, Bordeaux50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Systemic Lupus Erythematosus

Interventions

blood sampleBIOLOGICAL

30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patient aged over 18 years old * Diagnosis of systemic lupus erythematosus * Affiliated person or beneficiary of a social security scheme. * Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research). 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)

Locations (1)

CHU de Bordeaux - Service d'Immunologie et Immunogénétique

Bordeaux, France

Outcomes

Primary Outcomes

Quantification of O-GlcNAcylation level in the blood samples of SLE

Time frame: At baseline (Day 0)

Secondary Outcomes

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.

Time frame: At baseline (Day 0)

Disease activity according to British Lupus Assessment Group Index 2004 (BILAG-2004)

(Min value : 0 - Max value : 4), with higher values mean more severe symptoms

Time frame: At baseline (Day 0)

Quantification of OGT biallelic expression in the blood samples of SLE

Time frame: At baseline (Day 0)

Data from ClinicalTrials.gov

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