An observational study in Systemic Lupus Erythematosus Nephritis, sponsored by University Hospital, Grenoble. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-28.
Sponsored by University Hospital, Grenoble · Observational
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.
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
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.
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.
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.
245 studies on the registry are indexed under Nephritis; 56 are open to participants now.
This study's enrollment of 4 is below the median of 90 across 69 observational studies indexed under Nephritis.
Browse Nephritis studies →University Hospital, Grenoble is the lead sponsor of 815 studies on the registry; 205 are open to participants now.
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SLE patients with lupus Nephritis
Inclusion Criteria:
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:
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
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.
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.
Time frame: Measure at day of inclusion = TO
Investigation of ficolin-3 deposition in renal biopsy of the same 14 patients with active LN.
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 +++).
Time frame: Measure at day of inclusion = TO
Quantification of anti-ficolin-3 antibodies.
Anti-ficolin-3 antibodies are quantified by ELISA. Results are given in Arbitrary Units (AU)
Time frame: Measure at day of inclusion = TO
Quantification of serum levels of ficolin-3.
Ficolin-3 is quantified by ELISA. Results are given in µg/mL.
Time frame: Measure at day of inclusion = TO
Correlation of anti-ficolin-3 antibodies and serum levels of ficolin-3.
Anti-ficolin-3 antibodies and ficolin-3 are quantified by ELISA.
Time frame: Measure at day of inclusion = TO
Correlation between serum levels of anti-ficolin-3 antibodies and ficolin-3 deposition in the kidney.
Serum levels of anti-ficolin-3 antibodies and ficolin-3 deposition in the kidney are quantified by ELISA.
Time frame: Measure at day of inclusion = TO
Correlation between serum levels of ficolin-3 and ficolin-3 deposition in the kidney.
Serum levels of ficolin-3 and ficolin-3 deposition in the kidney are quantified by ELISA.
Time frame: 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.
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.
Time frame: Measure at day of inclusion = TO
Investigation of ficolin-2 deposition in renal biopsy of the same 14 patients with active LN.
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 +++).
Time frame: Measure at day of inclusion = TO
Quantification of anti-ficolin-2 antibodies.
Anti-ficolin-2 antibodies are quantified by ELISA. Results are given in arbitrary units (AU).
Time frame: Measure at day of inclusion = TO
Quantification of serum levels of ficolin-2.
Ficolin-2 is quantified by ELISA. Results are given in µg/mL.
Time frame: Measure at day of inclusion = TO
Correlation between anti-ficolin-2 antibodies and serum levels of ficolin-2.
Anti-ficolin-2 antibodies and ficolin-2 are quantified by ELISA.
Time frame: Measure at day of inclusion = TO
Correlation between serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney.
Serum levels of anti-ficolin-2 antibodies and ficolin-2 deposition in the kidney are quantified by ELISA.
Time frame: Measure at day of inclusion = TO
Correlation between serum levels of ficolin-2 and ficolin-2 deposition in the kidney.
Serum levels of ficolin-2 and ficolin-2 deposition in the kidney are quantified by ELISA.
Time frame: Measure at day of inclusion = TO
Plan to share: No
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University Hospital, Grenoble