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

NCT ID: NCT05193591

Last Updated: 2024-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-03-11

Study Completion Date

2025-09-10

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.

Conditions

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Lupus Erythematosus, Systemic

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Interventions

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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.

Intervention Type OTHER

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Marseille

OTHER

Sponsor Role collaborator

University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chantal DUMESTRE-PERARD, Professor

Role: PRINCIPAL_INVESTIGATOR

Grenoble Alpes University Hospital

Locations

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CHU Grenoble Alpes

Grenoble, , France

Site Status RECRUITING

AP-HM_Hôpital de la Conception

Marseille, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Chantal DUMESTRE-PERARD, Professor

Role: CONTACT

0476765015

Giovanna CLAVARINO, Doctor

Role: CONTACT

0476766331

Facility Contacts

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Chantal DUMESTRE-PERARD

Role: primary

+33 (0)4 76 76 50 15

Noemie JOURDE-CHICHE

Role: primary

+33 (0)4 91 38 30 42

References

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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.

Reference Type BACKGROUND
PMID: 20010915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26941740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24531837 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27648302 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9574573 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25815344 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26913032 (View on PubMed)

Other Identifiers

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2021-A02672-39

Identifier Type: OTHER

Identifier Source: secondary_id

38RC21.0388

Identifier Type: -

Identifier Source: org_study_id

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