Glycosylation Analysis of Lupus Anti-DNA Antibodies (GALA)

NCT ID: NCT05394922

Last Updated: 2024-08-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 140 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-08-23
• Study Completion Date: 2027-02-22

Brief Summary

Systemic lupus erythematosus (SLE) is a severe autoimmune disease in which patients often develop numerous autoantibodies (Abs). Unfortunately, none of the SLE specific Abs described so far (anti-DNA, -C1q, -nucleosome) are correlated enough to the disease activity to be used as a useful biomarker and reliably help in the therapeutic decision.

Abs effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and antibody-mediated complement activation, are conditioned by the structure of the crystallizable fragment (Fc) and especially the N-linked oligosaccharide structures attached to the asparagine-297 in the CH2 domain of the Fc region. It has been shown that the decrease in galactosylation, sialylation and fucolylation is generally associated with inflammatory function of circulating IgG whereas Abs with sialic acid, fucose and/or galactose in Asn-297 are anti-inflammatory. This major role of Ab glycosylation in the regulation of the effector and pathogenic functions of Abs have been well documented in rheumatoid arthritis and ANCA associated vasculitis with a good correlation between Ab sialylation and disease activity. In lupus, it has been shown that glycosylation of total IgG is also altered and correlated with disease activity but glycosylation analysis of the LES specific Abs is still lacking.

The aim of this study is to analyse by mass spectrometry (MS) the different glycoforms of anti-DNA Abs in lupus patients and find a correlation with disease activity.

Detailed Description

140 adult patients with lupus and anti-DNA Abs will be prospectively recruited in the University Hospital of Montpellier and Nîmes (department of rheumatology, internal medicine and nephrology) and followed during 1 year.

Blood samples will be drawn at inclusion, at 1 year and during any flare of the disease. After centrifugation (2000g x 10 minutes) serum will be aliquoted and frozen at -80°C.

At the end of the study, total IgG will be isolated using protein G and anti-DNA Abs will be purified from total IgG with DNA affinity columns. Glycosylation status of the anti-DNA Abs will be extensively determined by mass spectrometry and correlated to disease activity (SLEDAI).

Conditions

Lupus Erythematosus Disseminatus; Autoimmune Diseases; Chronic Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients presenting with LED according to the ACR/EULAR 2019 criteria, all clinical forms combined, quiescent or in flare with positive native anti-DNA antibodies, providing oral informed consent.

Exclusion Criteria

• Patients under protection of justice or unable to receive a clear information.
• High probability of non-compliance with the protocol or withdrawal during the study
• Already involved in another interventional clinical study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Montpellier University Hospital

Montpellier, , France

Site Status: RECRUITING

Nimes University Hospital

Nîmes, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Thierry VINCENT, MD

Role: CONTACT

t-vincent@chu-montpellier.fr

+334 67 33 71 35

Radjiv GOULABCHAND, MD

Role: CONTACT

Radjiv.GOULABCHAND@chu-nimes.fr

+334 66 68 32 41

Facility Contacts

Guilpain

Role: primary

RADJIV GOULABCHAND

Role: primary

Other Identifiers

RECHMPL21_0404

Identifier Type: -

Identifier Source: org_study_id