Autoreactive B Cells in Membranous Nephropathy

NCT ID: NCT04095156

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 86 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-09-12
• Study Completion Date: 2026-03-31

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Prospective cohort

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

In vitro assays.

Intervention Type: DIAGNOSTIC_TEST

Biochemical and flow-cytometry analysis of specimen collected.

Retrospective cohort

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

In vitro assays.

Intervention Type: DIAGNOSTIC_TEST

Biochemical and flow-cytometry analysis of specimen collected.

Healthy volunteers cohort

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

In vitro assays.

Intervention Type: DIAGNOSTIC_TEST

Biochemical and flow-cytometry analysis of specimen collected.

Interventions

In vitro assays.

Biochemical and flow-cytometry analysis of specimen collected.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Ranica, BG, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Manuel Podestà, MD

Role: CONTACT

manuel.podesta@guest.marionegri.it

003903545351

Facility Contacts

Manuel Podesta, MD

Role: primary

Manuel.podesta@guest.marionegri.it

0039 035 45351

Other Identifiers

PEPTIDE

Identifier Type: -

Identifier Source: org_study_id