Clinical trial NCT05193591: Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in Systemic Lupus Erythematosus (DYSALARM-322)
Official title: Evaluation of Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in the Pathogenesis for Patients With Systemic Lupus Erythematosus (SLE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lupus Erythematosus, Systemic
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: University Hospital, Marseille
First posted: 2022-01-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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).

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Inclusion is the only visit (only one time point)
Secondary outcomes:
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU Grenoble Alpes
city: Marseille
country: France
facility: AP-HM_Hôpital de la Conception
Study officials:
affiliation: Grenoble Alpes University Hospital
name: Chantal DUMESTRE-PERARD, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.