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

September 27, 2021 updated by: University Hospital, Grenoble

Role of Anti-ficolin-3 Antibodies in the Pathogenesis of Lupus Nephritis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • La Tronche, France
        • JOUVE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

SLE patients with lupus Nephritis

Description

Inclusion Criteria:

  • Age ≥ 18 years old
  • Patients who have valid health insurance
  • Non-opposition to participation obtained
  • Diagnostic de lupus according to SLICC 2012, performed more than 3 months ago.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Measure at day of inclusion = TO

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 +++).
Measure at day of inclusion = TO
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)
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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 +++).
Measure at day of inclusion = TO
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).
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO
Correlation between serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney.
Time Frame: Measure at day of inclusion = TO
Serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney are quantified by ELISA.
Measure at day of inclusion = TO
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.
Measure at day of inclusion = TO

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Collaborators

Institut de Biologie Structurale Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2019

Primary Completion (Actual)

June 20, 2020

Study Completion (Actual)

June 20, 2020

Study Registration Dates

First Submitted

January 22, 2019

First Submitted That Met QC Criteria

February 12, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

September 28, 2021

Last Update Submitted That Met QC Criteria

September 27, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC18.303
  • 2018-A02942-53 (Other Identifier: ID RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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