O-GlcNAcylation Role in the Pathophysiology of Systemic Lupus Erythematosus (METABOLUPS)

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: blood sample

Detailed Description

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
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrick BLANCO, Prof; Phone Number: +33 (0)5 56 79 56 45; Email: patrick.blanco@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France
    • CHU de Bordeaux - Service d'Immunologie et Immunogénétique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Systemic lupus erythematosus (SLE)	Biological: blood sample; 30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantification of O-GlcNAcylation level in the blood samples of SLE	At baseline (Day 0)

Secondary Outcome Measures

Outcome Measure	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)	(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)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Patrick BLANCO, Prof, CHU Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Actual): February 14, 2022
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: June 17, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Systemic lupus erythematosus; autoimmunity; O-GlcNAcylation
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CHUBX 2020/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No