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

Membranous Nephropathy Clinical Trial

Official title:

Analysis of T- and B-Cell Subpopulations in Patients With Primary Membranous Nephropathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05894512
• Other study ID #: 2023/887
• Status: Active, not recruiting
• Start date: June 1, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: April 2024
• Source: Istanbul University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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. What is the relationship of these cell populations and their distribution during follow-up with treatment, treatment responses, and relapses?

2. What is the relationship of the cell populations with anti-PLA2R (or anti-THSD7A) antibody levels?

Participants will provide peripheral venous blood samples at pre-designated regular intervals.

The research team will compare results of the primary MN group with two control groups (IgA nephropathy and healthy volunteer groups) to see if the findings are specific for primary MN.

Description:

Primary membranous nephropathy (MN), which is one of the most common causes of nephrotic syndrome in adults, is an autoimmune disease characterized with remissions and exacerbations. About half of the patients who do not go into remission progress to end-stage kidney disease.

In recent years, a lot of progress has been made in the fields of nephrology and immunology regarding primary MN. The process, which began with the detection of autoantibodies against the M-type phospholipase A2 receptor (PLA2R) in approximately 70% of the patients, continued with the discovery of new molecules for diagnosis and follow-up. However, despite all these advances, studies based on the analysis of peripheral blood mononuclear cells in patients with primary MN are very few: Rosenzwajg et al. analyzed lymphocyte subgroups in 25 MN patients and 27 healthy controls, and showed that regulatory T cells were significantly decreased in patients, naive B cells were increased, and memory B cells were decreased (Rosenzwajg et al. Kidney Int 2017). In 2020, Cantarelli et al. performed an extensive analysis in 30 patients with MN, showing that regulator B cells were increased in the MN group (Cantarelli et al. Kidney Int Rep 2020). These studies were generally cross-sectional or sampling was performed at a maximum of 6 months of follow-up. More studies based on long-term follow-up are needed.

Therefore, the aim of this observational study is to provide analysis of T and B lymphocyte subgroups in peripheral blood samples of patients with primary 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. It is designed to investigate the relationship of these cell populations and their distribution during follow-up with treatment, treatment responses, and relapses. The relationship of cell populations with antibody levels over time will also be examined.

By investigating the distribution of T and B lymphocyte subgroups in patients with primary MN during the follow-up, and its relationship with treatment, treatment responses, and relapses, it is expected to better elucidate the pathogenesis of the disease and to detect cell changes suggestive of remission and recurrence.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• Refusing to participate in the research.

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Membranous Nephropathy

Locations

Country	Name	City	State
Turkey	Istanbul University	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Istanbul University

Country where clinical trial is conducted

Turkey, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum anti-PLA2R IgG antibody levels	Serum anti-PLA2R IgG antibody levels will be evaluated with enzyme-linked immunosorbent assay (ELISA) throughout the 2-year follow-up process.	2 years
Other	Serum anti-THSD7A IgG antibody levels	In PLA2R-negative patients, serum anti-THSD7A IgG antibody levels will be evaluated with indirect immunofluorescence test (IIFT) throughout the 2-year follow-up process.	2 years
Primary	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	Complete remission	Reduction of proteinuria to <0.3 g/g or g/day, stable serum creatinine, and serum albumin >3.5 g/dl.	2 years
Secondary	Partial remission	Reduction of proteinuria to 0.3-3.5 g/g or g/day with an at least a 50% decrease from the baseline.	2 years
Secondary	Relapse	Proteinuria of at least 3.5 g/g or g/day after complete or partial remission has been reached.	2 years
Secondary	Composite kidney outcome	Initiation of kidney replacement therapies (hemodialysis, peritoneal dialysis or kidney transplantation), development of stage 5 chronic kidney disease (eGFR <15 ml/min/1.73 m2), or at least a 50% loss in eGFR.	2 years