PLA2R Autoreactive B-Cell Subsets and Immune Cell Monitoring in Membranous Nephropathy: Identification of Outcome Predictors and Novel Insights Into Disease Pathogenesis

Status: Recruiting
Location: See location...
Intervention Type: Diagnostic test
Study Type: Observational
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: t
View:

⁃ Patients 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.

⁃ Healthy volunteers inclusion criteria

• 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

Locations
Other Locations
Italy
Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò
RECRUITING
Ranica
Contact Information
Primary
Manuel Podestà, MD
manuel.podesta@guest.marionegri.it
003903545351
Time Frame
Start Date: 2019-09-12
Estimated Completion Date: 2026-03
Participants
Target number of participants: 86
Treatments
Prospective cohort
Patients with biopsy-proven idiopathic MN, who are candidate to receive a B-cell depleting treatment as per center clinical practice.
Retrospective cohort
Patients with biopsy-proven idiopathic MN, who already received a B-cell depleting treatment as per center clinical practice.
Healthy volunteers cohort
Subjects \> 18 years not known to suffer of any significant illness, not assuming any medication or drug on a regular basis.
Sponsors
Leads: Mario Negri Institute for Pharmacological Research

This content was sourced from clinicaltrials.gov

Similar Clinical Trials