Analysis of T- and B-Cell Subpopulations in Membranous Nephropathy

NCT05894512 | Completed

• 1 other identifier: 2023/887
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this observational study is to provide analysis of T and B lymphocyte subgroups in peripheral blood samples of patients with primary membranous nephropathy (MN). A search for disease-related circulating antibodies \[anti-phospholipase A2 receptor antibody (anti-PLA2R) and anti-thrombospondin type 1 domain-containing 7A antibody (anti-THSD7A)\] in patients' sera is also planned. The main questions to answer are:

1. 1.What is the relationship of these cell populations and their distribution during follow-up with treatment, treatment responses, and relapses?
2. 2.What is the relationship of the cell populations with anti-PLA2R (or anti-THSD7A) antibody levels?

Conditions

Membranous Nephropathy; Membranous Nephropathy - PLA2R Induced; Membranous Nephropathy - THSD7A Induced

Keywords

membranous nephropathy; rituximab; flow cytometry; immunophenotyping; PLA2R

Outcome Measures

Primary Outcomes (1)

• Distribution of T- and B-cell subpopulations

  Distribution of T- and B-cell subpopulations will be evaluated with flow cytometry throughout the 2-year follow-up process.

  2 years

Secondary Outcomes (4)

• Complete remission

  2 years

• Partial remission

  2 years

• Relapse

  2 years

• Composite kidney outcome

  2 years

Other Outcomes (2)

• Serum anti-PLA2R IgG antibody levels

  2 years

• Serum anti-THSD7A IgG antibody levels

  2 years

Study Arms (3)

Study Group (Primary Membranous Nephropathy)

Patients with biopsy-proven primary membranous nephropathy will be included (n=18). Samples will be collected from patients diagnosed with primary MN before starting conventional immunosuppressive therapy with calcineurin inhibitors (CNI) and corticosteroids (CS) and at 3, 6, 12, 18 and 24 months after starting the treatment. In case of failure after treatment with CNIs and CS treatment, rituximab (RTX) is used. If patient switches to RTX, samples will be taken before and 1, 3, 6, 12, 18, and 24 months after the first dose of RTX. If relapse occurs, sampling will be done regardless of the timing. Treatment decisions will solely be made in line with the guidelines, and there will be no intervention.

Control Group 1 (IgA Nephropathy)

After the patient group sampling is completed, a diseased control group will be formed from patients with primary IgA nephropathy according to the distribution of age and sex (n=12). Samples will be collected from the patients for one time only (cross-sectional sampling).

Control Group 2 (Healthy Volunteers)

After the patient group sampling is completed, a healthy control group will be formed from healthy volunteers according to the distribution of age and sex (n=14). Samples will be collected from healthy volunteers for one time only (cross-sectional sampling).

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 membranous nephropathy (study group) and IgA nephropathy (control group).

You may qualify if:

• Having a diagnosis of primary membranous nephropathy (patient group).
• Having a diagnosis of primary IgA nephropathy (diseased control group).
• Being healthy (healthy control group).
• Agreeing to participate in the research (informed consent).

You may not qualify if:

• Refusing to participate in the research.

Sponsors & Collaborators

• Istanbul University: lead

Study Sites (1)

Istanbul University

Istanbul, Turkey (Türkiye)

Location

Related Publications (2)

• Rosenzwajg M, Languille E, Debiec H, Hygino J, Dahan K, Simon T, Klatzmann D, Ronco P. B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab. Kidney Int. 2017 Jul;92(1):227-237. doi: 10.1016/j.kint.2017.01.012. Epub 2017 Mar 15.

  PMID: 28318628 BACKGROUND

• Cantarelli C, Jarque M, Angeletti A, Manrique J, Hartzell S, O'Donnell T, Merritt E, Laserson U, Perin L, Donadei C, Anderson L, Fischman C, Chan E, Draibe J, Fulladosa X, Torras J, Riella LV, La Manna G, Fiaccadori E, Maggiore U, Bestard O, Cravedi P. A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients. Kidney Int Rep. 2020 Aug 1;5(10):1764-1776. doi: 10.1016/j.ekir.2020.07.028. eCollection 2020 Oct.

  PMID: 33102969 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral venous blood samples from the volunteers will be taken into 20 ml EDTA, heparinized and dry tubes. Blood samples taken into a 10 ml dry tube will be centrifuged at 3000 rpm for 10 minutes. After the process, the separated serum will be placed in Eppendorf tubes (microcentrifuge tubes) and frozen at -20°C for 48 hours, and then transferred to deep freezers to be stored at -80°C. Peripheral blood mononuclear cells (PBMCs) will be obtained from blood samples by Ficoll concentration gradient centrifugation method. PBMCs collected after centrifugation will be suspended with fetal bovine serum (FBS). Cells in FBS medium will be taken into cryotubes, frozen in liquid nitrogen (-196°C) by adding dimethyl sulfoxide and stored until the laboratory studies.

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

Study Officials

• Suzan Adin Cinar, PhD

  Istanbul University

  STUDY CHAIR

• Safak Mirioglu, MD

  Istanbul University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 8, 2023
• Study Start: June 1, 2023
• Primary Completion: February 15, 2026
• Study Completion: February 15, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)