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NCT Number: NCT05894512

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

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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Distribution of T- and B-cell subpopulations

    Time frame: 2 years

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

Secondary outcomes

  1. Complete remission

    Time frame: 2 years

    Reduction of proteinuria to <0.3 g/g or g/day, stable serum creatinine, and serum albumin >3.5 g/dl.

  2. Partial remission

    Time frame: 2 years

    Reduction of proteinuria to 0.3-3.5 g/g or g/day with an at least a 50% decrease from the baseline.

  3. Relapse

    Time frame: 2 years

    Proteinuria of at least 3.5 g/g or g/day after complete or partial remission has been reached.

  4. Composite kidney outcome

    Time frame: 2 years

    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.

Other outcomes

  1. Serum anti-PLA2R IgG antibody levels

    Time frame: 2 years

    Serum anti-PLA2R IgG antibody levels will be evaluated with enzyme-linked immunosorbent assay (ELISA) throughout the 2-year follow-up process.

  2. Serum anti-THSD7A IgG antibody levels

    Time frame: 2 years

    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.

Sponsors and collaborators

Lead sponsor

Istanbul University

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Jun 8, 2023
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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