Autoreactive B Cells in Membranous Nephropathy

NCT04095156 | Recruiting

• 1 other identifier: PEPTIDE
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome (NS) in adults. The majority of MN patients show detectable circulating antibodies against the M-type phospholipase A2 receptor (PLA2R). Infusion of anti-CD20 monoclonal antibodies results in a profound depletion of B-cells, which are thought to be responsible for anti-PLA2R production. B-cell depletion is followed by NS remission in 70% of cases. Limited evidence highlighted that differences in the B- and T-cell compartments may exist between responders and non-responders. Owing to the non-homogenous efficacy of anti-CD20 treatment, investigators hypothesize that in MN patients who experience NS remission after B-cell depleting therapy, autoreactive B-cells may be mostly circulating, whereas in patients who do not respond to the same treatment, autoreactive B-cells may chiefly reside into secondary lymphoid organs - and thus be more resistant to the drug action. Researchers will therefore extensively analyze the circulating immune repertoire of MN patients before and after the infusion of B-cell lineage depleting agents, assessing the presence of circulating PLA2R autoreactive B cells from appropriately stratified responder and non-responder patients. Patients and healthy controls will be enrolled in this study. Patients will be stratified according to gender, anti-PLA2R status, type of B-cell lineage depleting agent received and response to treatment.

Conditions

Membranous Nephropathy

Keywords

Membranous nephropathy; B cells; Anti-PLA2R; Anti-CD20 antibodies

Outcome Measures

Primary Outcomes (5)

• Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of anti-PLA2R autoreactive circulating B-cells.

  Changes from baseline and 3,6,9,12 and 24 month.

• Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of immunoglobulin- and cytokine-secreting circulating B-cell subsets in resting and stimulated conditions.

  Changes from baseline and 3,6,9,12 and 24 month.

• Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in spontaneous / stimulated immunoglobulin (including anti-PLA2R) and cytokine release from circulating B-cell subpopulations.

  Changes from baseline and 3,6,9,12 and 24 month.

• Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating B-cell subpopulations.

  Changes from baseline and 3,6,9,12 and 24 month.

• Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating T-cell, NK-cell, monocyte and dendritic cell subpopulations.

  Changes from baseline and 3,6,9,12 and 24 month.

Study Arms (3)

Prospective cohort

Patients with biopsy-proven idiopathic MN, who are candidate to receive a B-cell depleting treatment as per center clinical practice.

Diagnostic Test: In vitro assays.

Retrospective cohort

Patients with biopsy-proven idiopathic MN, who already received a B-cell depleting treatment as per center clinical practice.

Diagnostic Test: In vitro assays.

Healthy volunteers cohort

Subjects \> 18 years not known to suffer of any significant illness, not assuming any medication or drug on a regular basis.

Diagnostic Test: In vitro assays.

Interventions

In vitro assays. DIAGNOSTIC_TEST

Biochemical and flow-cytometry analysis of specimen collected.

Healthy volunteers cohort; Prospective cohort; Retrospective cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with biopsy-proven idiopathic MN, who are candidate to receive (prospective cohort) or who already received (retrospective cohort) a B-cell depleting treatment as per center clinical practice and healthy volunteers as controls

You may qualify if:

• Males and females.
• Adults (\> 18 years old).
• Patients with biopsy-proven idiopathic MN, who are candidate to receive (prospective cohort) or who already received (retrospective cohort) a B-cell depleting treatment as per center clinical practice.
• Mental state is such that they are able to understand and give valid consent to the study;
• Written informed consent according to the guidelines of the Declaration of Helsinki.
• Male and female (\>18 years) not known to suffer of any significant illness;
• Not assuming any medication or drug on a regular basis;
• Negative urine analysis (urine dipstick, multistick);
• Written informed consent according to the guidelines of the Declaration of Helsinki

You may not qualify if:

• Reasonable possibility of a secondary cause of MN (e.g.systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine).
• Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.
• \- Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Centro di Ricerche Cliniche per le Malattie Rare " Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

A research biobank will be established at "Centro di Risorse Biologiche Mario Negri - Biobanca Malattie Rare" containing biological material in the form serum and peripheral blood mononuclear cell (PBMC) samples.

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Manuel Podestà, MD

CONTACT

003903545351; manuel.podesta@guest.marionegri.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 19, 2019
• Study Start: September 25, 2019
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

IT (1)