NCT05193591

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

Evaluation of Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in the Pathogenesis for Patients With Systemic Lupus Erythematosus (SLE)

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 30 (estimated)
• Sponsor: University Hospital, Grenoble · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Regarding the exploration of anti-C1s autoantibodies purified from the SLE patients' serum, the investigators will evaluate their effects on the formation of the C1r2C1s2 tetramer and interaction with C1q and their effects on the esterase activity of C1s. Regarding the exploration of anti-HMGB1 autoantibodies purified from the SLE patients' serum, the investigators will evaluate their effects on the binding of HMGB1 to its RAGE receptor and their effects on the binding of HMGB1 to C1q. Regarding the exploration of anti-C1q autoantibodies purified from the SLE patients' serum, the investigators will evaluate their effects on the binding of C1q to its receptors and to the C1r2C1s2 tetramer and their effects on the activation of the classical Complement pathway.

Conditions

• Lupus Erythematosus, Systemic

Interventions

Type	Name	Description
OTHER	Autoantibodies evaluation in lupus	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.

Timeline

• Start date: 2022-03-11
• Primary completion: 2025-09-10
• Completion: 2025-09-10
• First posted: 2022-01-18
• Last updated: 2024-08-30

Locations

2 sites across 1 country: France