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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Other: Autoantibodies evaluation in lupus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |