Lupus Erythematosus, SystemicDYSALARM-322NCT05193591
Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in Systemic Lupus Erythematosus (DYSALARM-322)
An observational study of Lupus Erythematosus, Systemic, run by University Hospital, Grenoble at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Erythematosus, Systemic
- What is being tested?
- Autoantibodies evaluation in lupus
- How many people
- 30 participants
- Where
- 2 sitesFrance
- Study dates
- 11 Mar 2022to 10 Sep 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
France2 sites, 2 recruiting
- Recruiting
CHU Grenoble Alpes
Grenoble, 38043
Chantal DUMESTRE-PERARD, +33 (0)4 76 76 50 15, CDumestre-Perard@chu-grenoble.fr
- Recruiting
AP-HM_Hôpital de la Conception
Marseille, 13005
Noemie JOURDE-CHICHE, +33 (0)4 91 38 30 42, Noemie.JOURDE@ap-hm.fr
About this study
Official title: Evaluation of Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in the Pathogenesis for Patients With Systemic Lupus Erythematosus (SLE)
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.
Read more
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.
Read the 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
- Being tested
- Autoantibodies evaluation in lupus
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autoantibodies evaluation in lupusOther
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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Inclusion is the only visit (only one time point)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2022
- Study start11 Mar 2022
- Primary completion10 Sep 2025 (estimated)
- Study completion10 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Marseille
- Responsible party
- Sponsor
- Investigators
- Chantal DUMESTRE-PERARD, Professor, Principal investigator, Grenoble Alpes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05193591
- Sponsor's protocol ID
- 38RC21.0388
- Other IDs
- 2021-A02672-39
- Acronym
- DYSALARM-322
- Status last verified
- Aug 2024
- First submitted
- 2 Dec 2021
- Last updated
- 30 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 20010915Macedo 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.
PubMed 26941740Schaper 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.
PubMed 24531837Yeo 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.
PubMed 27648302He 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.
PubMed 9574573Moroni 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.
PubMed 25815344Lintner 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.
PubMed 26913032
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Anti-C1s, Anti-HMGB1 and Anti-C1q Autoantibodies in the Pathogenesis for Patients With Systemic Lupus Erythematosus (SLE)
- ClinicalTrials.gov ID
- NCT05193591
- Acronym / sponsor ID
- DYSALARM-322 / 38RC21.0388
- Conditions
- Lupus Erythematosus, Systemic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- University Hospital, Marseille
- Study start
- 11 Mar 2022 (actual)
- Primary completion
- 10 Sep 2025 (estimated)
- Study completion
- 10 Sep 2025 (estimated)
- First posted
- 18 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autoantibodies evaluation in lupusBiological 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. | Other | – |
Primary outcome
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.
Time frame: Inclusion is the only visit (only one time point)
Analysis: Levels of anti-C1s autoantibodies targeting N-terminal, C-terminal domains and C1s protease mutants by homemade ELISA.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2024.
- Background: PubMed 20010915Dunkelberger 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.
- Background: PubMed 26941740Macedo 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.
- Background: PubMed 24531837Schaper 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.
- Background: PubMed 27648302Yeo 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.
- Background: PubMed 9574573He 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.
- Background: PubMed 25815344Moroni 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.
- Background: PubMed 26913032Lintner 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chantal DUMESTRE-PERARD, Professor principal investigator
Grenoble Alpes University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lupus Erythematosus, Systemic, run by University Hospital, Grenoble at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chantal DUMESTRE-PERARD, Professor (0476765015, cdumestre-perard@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Inclusion is the only visit (only one time point)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05193591, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2024.