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Trial record 5 of 907 for:    Lupus

Anti-ficolin-3 Antibodies in Lupus Nephritis (IgFicoLupus)

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ClinicalTrials.gov Identifier: NCT03842787
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : April 22, 2019
Sponsor:
Collaborator:
Institut de Biologie Structurale Grenoble
Information provided by (Responsible Party):
University Hospital, Grenoble

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. Although the underlying mechanisms are complex, defects in dying cells elimination are likely to contribute to autoantigen overload and development of autoimmunity. Molecules important in damaged cell clearance, such as early complement components, may thus have a protective role. According to this hypothesis, deficiencies in C1q and MBL, the recognition proteins of the classical and lectin pathways of complement; are associated with increased susceptibility to SLE. In the proposed project, the investigators will investigate the involvement of another related recognition protein, ficolin-3, which activates the complement lectin pathway and recognizes necrotic cells. The investigators have shown in a recent study a significant association between the presence of anti-ficolin-3 antibodies and active nephritis in patients with SLE. However, the possible involvement of anti-ficolin-3 antibodies in the pathogenesis of SLE and particularly in lupus nephritis (LN) remains to be elucidated. This project plans to investigate the role of ficolin-3 and ficolin-3 autoantibodies in LN. The study associates two aspects, aiming at deciphering the role of anti-ficolin-3 antibodies in dying cells recognition and investigating the role of ficolin-3 in renal tissue damage. This pilot study will be performed for 14 patients with active LN on serum and renal biopsy, realized for routine patient care. The investigators will explore the effect of anti-ficolin-3 antibodies purified from the patient serum on ficolin-3-dependent necrotic cells recognition, in relation with possible altered clearance of dead cells, which is an important hypothesis of the pathogenesis of SLE. The investigators will also investigate ficolin-3 deposition in renal biopsy, which may contribute to the local formation of immune complexes, leading to complement activation and subsequent inflammation and tissue injury.

Condition or disease Intervention/treatment
Systemic Lupus Erythematosus Nephritis Other: Biological analysis

Detailed Description:

PRIMARY OUTCOME MEASURE Exploration of the inhibition of anti-ficolin-3 antibodies purified from the serum of 14 patients with active lupus nephritis in ficolin-3-dependent necrotic cells recognition.

The criterion used is the shift of MFI (Mean Fluorescence Intensity) measured after addition of these antibodies to necrotic Jurkat cells incubated with ficolin-3.

The study has a single visit approach with serum collection, so every outcome is measured at T0, which is the only visit for the patient.

SECONDARY OUTCOME MEASURES

  1. Investigation of ficolin-3 deposition in renal biopsy of the same 14 patients with active LN.

    Analysis: deposition of ficolin-3 will be evaluated by immunostaining on renal biopsy.

  2. Quantification of anti-ficolin-3 antibodies. Analysis: Anti-ficolin-3 antibodies are quantified by ELISA.
  3. Quantification of serum levels of ficolin-3. Analysis: Ficolin-3 is quantified by ELISA.
  4. Correlation between anti-ficolin-3 antibodies and serum levels of ficolin-3. Analysis: Anti-ficolin-3 antibodies and ficolin-3 are quantified by ELISA.
  5. Correlation between serum levels of anti-ficolin-3 antibodies and ficolin-3 deposition in the kidney.
  6. Correlation between serum levels of ficolin-3 and ficolin-3 deposition in the kidney.
  7. Exploration of the inhibition of anti-ficolin-2 antibodies purified from the serum of 14 patients with active lupus nephritis in ficolin-2-dependent necrotic cells recognition.

    The criterion used is the shift of MFI (Mean Fluorescence Intensity) measured after addition of these antibodies to necrotic Jurkat cells incubated with ficolin-2.

  8. Investigation of ficolin-2 deposition in renal biopsy of the same 14 patients with active LN.

    Analysis: deposition of ficolin-2 will be evaluated by immunostaining on renal biopsy.

  9. Quantification of anti-ficolin-2 antibodies. Analysis: Anti-ficolin-2 antibodies are quantified by ELISA.
  10. Quantification of serum levels of ficolin-2. Analysis: Ficolin-2 is quantified by ELISA.
  11. Correlation between anti-ficolin-2 antibodies and serum levels of ficolin-2. Analysis: Anti-ficolin-2 antibodies and ficolin-2 are quantified by ELISA.
  12. Correlation between serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney.
  13. Correlation between serum levels of ficolin-2 and ficolin-2 deposition in the kidney.

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Study Type : Observational
Estimated Enrollment : 14 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Role of Anti-ficolin-3 Antibodies in the Pathogenesis of Lupus Nephritis
Actual Study Start Date : March 7, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : January 2021


Group/Cohort Intervention/treatment
SLE patients with lupus Nephritis

14 SLE patients with lupus Nephritis

Biological analysis and biopsy were (routinely) performed

Ethics The protocol will be submitted to a randomly chosen Institutional Review Board (Comité de Protection des Personnes), in compliance to French regulation.

Investigators will include patients followed for routine care. Patients will be informed that samples (serum and kidney biopsy) that are performed for routine patient care will subsequently be used for research purposes, with no additional blood draw/biopsy. They will sign informed consent.

Other: Biological analysis

Biological and research analysis:

Quantification of ficolin-3, anti-ficolin-3 antibodies, ficolin-2, anti-ficolin-2 antibodies

Purification of patients' antibodies (anti-ficolin-3 and -2)

Evaluation of effects of anti-ficolin-3 and anti-ficolin-2 purified antibodies Investigation of ficolin-3 and ficolin-2 deposition in renal biopsy





Primary Outcome Measures :
  1. Exploration of the inhibition of anti-ficolin-3 antibodies purified from the serum of 14 patients with active lupus nephritis in ficolin-3-dependent necrotic cells recognition. [ Time Frame: Measure at day of inclusion = TO ]
    In order to investigate the possible interference of the anti-ficolin-3 antibodies purified from patients'sera with ficolin-3 dependent necrotic cells recognition, recombinant ficolin-3 will be preincubated with the purified specific autoantibodies before addition to Jurkat necrotic cells. Ficolin-3 binding will be measured using the flow cytometry and immunofluorescence assays described above and quantified using the mean fluorescence intensity (MFI). The criterion used is the shift of MFI (Mean Fluorescence Intensity) measured after addition of these antibodies to necrotic Jurkat cells incubated with ficolin-3.


Secondary Outcome Measures :
  1. Investigation of ficolin-3 deposition in renal biopsy of the same 14 patients with active LN. [ Time Frame: Measure at day of inclusion = TO ]
    The investigators will investigate the presence of ficolin-3 in the glomeruli by direct immunofluorescence analysis. They search deposits in the interstitial vessels, interstitium and glomeruli (mesangium, extra-membranous, glomerular basement membrane) and quantify them semi-quantitatively (+, ++ or +++).

  2. Quantification of anti-ficolin-3 antibodies. [ Time Frame: Measure at day of inclusion = TO ]
    Anti-ficolin-3 antibodies are quantified by ELISA. Results are given in Arbitrary Units (AU)

  3. Quantification of serum levels of ficolin-3. [ Time Frame: Measure at day of inclusion = TO ]
    Ficolin-3 is quantified by ELISA. Results are given in µg/mL.

  4. Correlation of anti-ficolin-3 antibodies and serum levels of ficolin-3. [ Time Frame: Measure at day of inclusion = TO ]
    Anti-ficolin-3 antibodies and ficolin-3 are quantified by ELISA.

  5. Correlation between serum levels of anti-ficolin-3 antibodies and ficolin-3 deposition in the kidney. [ Time Frame: Measure at day of inclusion = TO ]
    Serum levels of anti-ficolin-3 antibodies and ficolin-3 deposition in the kidney are quantified by ELISA.

  6. Correlation between serum levels of ficolin-3 and ficolin-3 deposition in the kidney. [ Time Frame: Measure at day of inclusion = TO ]
    Serum levels of ficolin-3 and ficolin-3 deposition in the kidney are quantified by ELISA.

  7. Exploration of the inhibition of anti-ficolin-2 antibodies purified from the serum of 14 patients with active lupus nephritis in ficolin-2-dependent necrotic cells recognition. [ Time Frame: Measure at day of inclusion = TO ]
    In order to investigate the possible interference of the anti-ficolin-2 antibodies purified from patients'sera with ficolin-2 dependent necrotic cells recognition, recombinant ficolin-2 will be preincubated with the purified specific autoantibodies before addition to Jurkat necrotic cells. Ficolin-2 binding will be measured using the flow cytometry and immunofluorescence assays described above and quantified using the mean fluorescence intensity (MFI). The criterion used is the shift of MFI (Mean Fluorescence Intensity) measured after addition of these antibodies to necrotic Jurkat cells incubated with ficolin-2.

  8. Investigation of ficolin-2 deposition in renal biopsy of the same 14 patients with active LN. [ Time Frame: Measure at day of inclusion = TO ]
    The investigators will investigate the presence of ficolin-2 in the glomeruli by direct immunofluorescence analysis. They search deposits in the interstitial vessels, interstitium and glomeruli (mesangium, extra-membranous, glomerular basement membrane) and quantify them semi-quantitatively (+, ++ or +++).

  9. Quantification of anti-ficolin-2 antibodies. [ Time Frame: Measure at day of inclusion = TO ]
    Anti-ficolin-2 antibodies are quantified by ELISA. Results are given in arbitrary units (AU).

  10. Quantification of serum levels of ficolin-2. [ Time Frame: Measure at day of inclusion = TO ]
    Ficolin-2 is quantified by ELISA. Results are given in µg/mL.

  11. Correlation between anti-ficolin-2 antibodies and serum levels of ficolin-2. [ Time Frame: Measure at day of inclusion = TO ]
    Anti-ficolin-2 antibodies and ficolin-2 are quantified by ELISA.

  12. Correlation between serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney. [ Time Frame: Mesure at day of inclusion = TO ]
    Serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney are quantified by ELISA.

  13. Correlation between serum levels of ficolin-2 and ficolin-2 deposition in the kidney. [ Time Frame: Measure at day of inclusion = TO ]
    Serum levels of ficolin-2 and ficolin-2 deposition in the kidney are quantified by ELISA.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
SLE patients with lupus Nephritis
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old
  • Patients who have valid health insurance
  • Non-opposition to participation obtained
  • Diagnostic de lupus selon SLICC 2012, effectué depuis plus de 3 mois.
  • Active lupus nephritis defined by :

elevated SLEDAI indexes (≥ 4), the presence of a significant proteinuria (≥ 0.5 g/day) and/or the presence of hematuria, aseptic leukocyturia or urinary casts, and documented by renal biopsy and classified according to the ISN/RPS classification.

Non-inclusion Criteria:

  • Patient with a known progressing cancer
  • Patient who had started lupus nephritis flare treatment
  • Participant involved in another interventional clinical study
  • Person deprived of liberty by judicial order
  • Person under guardianship or curatorship
  • Hemoglobin level < 7 g/dL

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03842787


Contacts
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Contact: Chantal DUMESTRE-PERARD, PHD +33 4 76 76 50 15 cdumestre-perard@chu-grenoble.fr

Locations
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France
JOUVE Recruiting
La Tronche, France
Contact: Chantal DUMESTRE-PERARD, PHD       cdumestre-perard@chu-grenoble.fr   
Sponsors and Collaborators
University Hospital, Grenoble
Institut de Biologie Structurale Grenoble

Publications:

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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT03842787     History of Changes
Other Study ID Numbers: 38RC18.303
2018-A02942-53 ( Other Identifier: ID RCB )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Grenoble:
systemic lupus erythematosus
lupus nephritis
complement
ficolin-3
anti-ficolin-3 autoantibodies
Additional relevant MeSH terms:
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Lupus Nephritis
Lupus Erythematosus, Systemic
Nephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs