Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in Systemic Lupus Erythematosus (DYSALARM-322)

NCT05193591 | Recruiting DMC

• 2 other identifiers: 38RC21.03882021-A02672-39
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies and accumulation of immune complexes resulting in systemic inflammatory response and tissue damage. Dysfunction of proteins initially known to initiate the classical pathway for complement activation (C1q and C1s), and their functional interference with the multifunctional protein HMGB1 (High-Mobility Group Box 1), appears to be associated with SLE. On the other hand, C1s, HMGB1 and C1q can be targeted by anti-C1s, anti-HMGB1 and anti-C1q autoantibodies from lupus patients, whose functional impact remains to be explored, in particular for non-canonical functions, independent of the complement activation cascade. Studies are needed to investigate the pathogenic role of these autoantibodies in SLE, including possible interference with the inactivation of HMGB1. This project plans to investigate the role of anti-C1s, anti-HMGB1 and anti-C1q autoantibodies in the pathogenesis of Systemic Lupus Erythematosus. This pilot study will be performed for 30 patients with active SLE on serum, realized for routine patient care. The investigators will identify the molecular targets recognized by anti-C1s, anti-HMGB1 and anti-C1q autoantibodies purified from the SLE patients' serum. The investigators will also explore the functional role of these purified autoantibodies.

Conditions

Lupus Erythematosus, Systemic

Outcome Measures

Primary Outcomes (1)

• Quantification of anti-C1s autoantibodies purified from the serum of lupus patients with active disease, targeting N-terminal, C-terminal domains and C1s protease mutants.

  Analysis: Levels of anti-C1s autoantibodies targeting N-terminal, C-terminal domains and C1s protease mutants by homemade ELISA.

  Inclusion is the only visit (only one time point)

Interventions

Autoantibodies evaluation in lupus OTHER

Biological analysis: anti-C1s, anti-HMGB1 and anti-C1q autoantibodies; C1s, HMGB1 and C1q proteins. Purification of patients' autoantibodies (anti-C1s, anti-HMGB1and anti-C1q). Identification of the molecular targets recognized by anti-C1s, anti-HMGB1 and anti-C1q autoantibodies purified from the SLE patients' serum.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients: 30 patients with active lupus (joint and/or kidney involvement). SLE patients will be enrolled from departments of Internal Medicine (Grenoble University Hospital, France) and Nephrology (Conception University Hospital Marseille, France).

You may qualify if:

• Age ≥ 18 years old
• Weight ≥ 40 Kg
• Patients who have valid health insurance
• Patients with lupus diagnosis criteria (EULAR-ACR-2019)
• Active lupus nephritis defined by SLEDAI score \>5 and joint and/or kidney involvement.

You may not qualify if:

• Patient protected by law (minors, pregnant or breastfeeding women, subject under guardianship or curatorship, deprived of liberty or enforced hospitalized, under administrative or judicial supervision).
• Patient on dialysis or on plasma exchange.

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• University Hospital, Marseille: collaborator

Study Sites (2)

CHU Grenoble Alpes

Grenoble, 38043, France

RECRUITING

AP-HM_Hôpital de la Conception

Marseille, 13005, France

RECRUITING

Related Publications (7)

• Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Res. 2010 Jan;20(1):34-50. doi: 10.1038/cr.2009.139. Epub 2009 Dec 15.

  PMID: 20010915 BACKGROUND

• Macedo AC, Isaac L. Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway. Front Immunol. 2016 Feb 24;7:55. doi: 10.3389/fimmu.2016.00055. eCollection 2016.

  PMID: 26941740 BACKGROUND

• Schaper F, Westra J, Bijl M. Recent developments in the role of high-mobility group box 1 in systemic lupus erythematosus. Mol Med. 2014 Mar 13;20(1):72-9. doi: 10.2119/molmed.2014.00019.

  PMID: 24531837 BACKGROUND

• Yeo JG, Leong J, Arkachaisri T, Cai Y, Teo BH, Tan JH, Das L, Lu J. Proteolytic inactivation of nuclear alarmin high-mobility group box 1 by complement protease C1s during apoptosis. Cell Death Discov. 2016 Sep 12;2:16069. doi: 10.1038/cddiscovery.2016.69. eCollection 2016.

  PMID: 27648302 BACKGROUND

• He S, Lin YL. In vitro stimulation of C1s proteolytic activities by C1s-presenting autoantibodies from patients with systemic lupus erythematosus. J Immunol. 1998 May 1;160(9):4641-7.

  PMID: 9574573 BACKGROUND

• Moroni G, Quaglini S, Radice A, Trezzi B, Raffiotta F, Messa P, Sinico RA. The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy. J Immunol Res. 2015;2015:106904. doi: 10.1155/2015/106904. Epub 2015 Feb 26.

  PMID: 25815344 BACKGROUND

• Lintner KE, Wu YL, Yang Y, Spencer CH, Hauptmann G, Hebert LA, Atkinson JP, Yu CY. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Front Immunol. 2016 Feb 15;7:36. doi: 10.3389/fimmu.2016.00036. eCollection 2016.

  PMID: 26913032 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

One serum sample per patient

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Chantal DUMESTRE-PERARD, Professor

  Grenoble Alpes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chantal DUMESTRE-PERARD, Professor

CONTACT

0476765015; cdumestre-perard@chu-grenoble.fr

Giovanna CLAVARINO, Doctor

CONTACT

0476766331; gclavarino@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: January 18, 2022
• Study Start: March 11, 2022
• Primary Completion: September 10, 2025
• Study Completion: September 10, 2025
• Last Updated: August 30, 2024

Record last verified: 2024-08

Locations

FR (2)