NCT05712369

B Cells in Idiopathic Nephrotic Syndrome

Phenotype and Function of Reconstituting B-cells in Steroid Dependent or Frequently Relapsing Nephrotic Syndrome After B-cell Depletion: Insight Into the Disease Pathogenesis and Identification of Predictors of Relapse

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Mario Negri Institute for Pharmacological Research · Academic / Other
• Sex: All
• Age: 6 Years
• Healthy volunteers: Accepted

Summary

The main aim of the present study is to determine whether reconstitution of different B-cell subpopulations can predict relapse after treatment with B-cell depleting antibodies in adult with NS, and whether specific B- or T-cell anomalies (as well as dysregulation of other circulating immune cell subsets) may play a role in the disease pathogenesis of SDNS and FRNS.

Detailed description

The role of the immune system in Idiopathic Nephrotic Syndrome (INS) of Minimal Change Disease (MCD), Mesangial proliferative Glomerulonephritis (MesGN) or Focal and Segmental Glomerulosclerosis (FSGS) has been widely investigated. However, among immune cell populations, a major player in disease pathogenesis was never found. The efficacy of B cell depleting therapy with anti-CD20 monoclonal antibodies suggests that B lymphocytes may play a pivotal role. Preliminary data suggest that memory B cells may be the responsible of the Nephrotic Syndrome (NS) relapse after rituximab treatment in children with Steroid Dependent Nephrotic Syndrome (SDNS) or Frequently-Relapsin gnephrotic Syndrome (FRNS), enforcing the role of the B cell lineage in the disease pathogenesis. NS is a severe glomerular disease affecting more frequently children and young adult. It is characterized by edema, heavy proteinuria and hypoalbuminemia, the clinical counterpart of the alteration of the selective glomerular permeability barrier. Despite extensive investigation, the mechanism and the immune cell population responsible for the disruption of glomerular filtration barrier and, consequently, of the development of proteinuria is still not clearly defined. However, the efficacy of the different immunosuppressive approaches including prednisone and anti-CD20 antibodies in the treatment of NS strongly suggests a central role of the immune system, in particular the role of B cells in the pathogenesis SDNS. Recent evidence indicates that, after B cell depletion, the delayed reconstitution of the switched memory B cells in children with SDNS was significantly and independently protective against relapse. These results suggest that recovery of switched memory B-cells after anti-CD20 therapies could be a useful predictor of subsequent relapse of the NS in SDNS and FRNS patients, and that memory B-cells may play a role in the pathogenesis of SDNS or FRNS in children.

Conditions

• Nephrotic Syndrome

Interventions

Type	Name	Description
OTHER	Blood sampling	Before the anti-CD20 monoclonal antibodies treatment (e.g. Rituximab/Ofatumumab) and after 6, 9 and 12, 24 months from the first infusion the following blood samples will be collected for the analysis of lymphocyte subpopulations: * 50/100 mL of blood (20 mL for pediatric patients) for Peripheral Blood Mononuclear Cells (PBMCs) isolation. * 8 mL of blood (both adult and pediatric) to obtain serum. Serum will be obtained by standard centrifugation and PBMC will be isolated by Ficoll-Paque® density gradient centrifugation, according to manufacturer's instruction.

Timeline

• Start date: 2019-04-02
• Primary completion: 2024-11-07
• Completion: 2024-11-07
• First posted: 2023-02-03
• Last updated: 2024-11-29

Locations

1 site across 1 country: Italy