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NCT Number: NCT07811557

Single-cell RNA Sequencing (scRNA-seq) to Investigate the Mechanisms Underlying the Induction of Regulatory T Cells in Patients With Extramembranous Glomerulonephritis Treated With Rituximab

Membranous nephropathy is a rare autoimmune kidney disease in which autoantibodies, most commonly anti-PLA2R1 antibodies, target podocyte antigens and may cause nephrotic syndrome. Rituximab is used in routine care to deplete B cells and reduce pathogenic autoantibodies, but its effects are not limited to B-cell depletion. Previous work suggests that rituximab may also promote regulatory T-cell (Treg) responses, and higher Treg levels after treatment have been associated with clinical remission.

TRANSCRIPT is a prospective, single-center, pilot mechanistic study in 12 adult patients with active anti-PLA2R1-positive membranous nephropathy who have an indication for rituximab as part of routine care. Participants will receive rituximab according to usual clinical practice (1 g on Day 0 and 1 g on Day 15). Additional blood samples will be collected at Day 0 and Month 6 to isolate peripheral immune cells. Single-cell RNA sequencing will be used to identify transcriptional changes, signaling pathways, and intercellular communication networks associated with rituximab-induced Treg induction. In vitro assays will then test modulators of the candidate pathways identified by sequencing.

The study hypothesis is that rituximab modulates immune-cell signaling and communication pathways that contribute to the induction of regulatory T cells in patients with membranous nephropathy.

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Key information

Conditions

Membranous Nephropathy Autoimmune Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Glomerulonephritis, Membranous Immune System Diseases Kidney Diseases Male Urogenital Diseases Membranous Nephropathy - PLA2R Induced Nephritis Nephrosis Nephrotic Syndrome Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Signed informed consent.
  • Anti-PLA2R1-positive membranous nephropathy.
  • Active nephrotic syndrome, defined as urinary protein/creatinine ratio >3.5 g/g and serum albumin <30 g/L.
  • Indication for rituximab treatment as part of routine care.
  • Estimated glomerular filtration rate calculated using the CKD-EPI equation >30 mL/min/1.73 m2.

Exclusion criteria

  • Lack of affiliation to the French social security system.
  • Vulnerable person, including minors, adults under guardianship or curatorship, pregnant women, persons deprived of liberty, or persons who do not master the French language.
  • Immunosuppressive treatment received within the previous 6 months.
  • Breastfeeding.
  • Absence of effective contraception, when applicable.
  • Premature discontinuation before administration of both rituximab infusions.
  • Voluntary withdrawal of informed consent or objection to the use of study data or biological samples.

Treatment and study plan

Peripheral blood immune-cell profiling by single-cell RNA sequencing and in vitro pathway modulation assays

Other

Participants with active anti-PLA2R1-positive membranous nephropathy and a routine-care indication for rituximab will undergo two additional research blood collections: one at Day 0 before or on the day of the first rituximab infusion, and one at Month 6. Peripheral blood mononuclear cells will be isolated, cryopreserved, and analyzed by single-cell RNA sequencing. Candidate signaling pathways associated with regulatory T-cell induction will be assessed in vitro using pathway activators or inhibitors and flow cytometry-based Treg measurement. Rituximab itself is administered as part of usual care at 1 g on Day 0 and 1 g on Day 15, not as an investigational treatment assigned by the study.

Primary outcomes

  1. Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6

    Time frame: Day 0 to Month 6

    Regulatory T-cell induction will be assessed by single-cell RNA sequencing of peripheral immune cells collected from 12 rituximab-treated participants at Day 0 and Month 6. The analysis will identify differentially expressed genes and their fold changes within immune-cell subpopulations, including Treg cells and partner immune-cell populations. It will also identify the main signaling and cell-cell communication pathways that are deregulated or modulated between Day 0 and Month 6.

Secondary outcomes

  1. In vitro induction of regulatory T cells by modulators of rituximab-associated signaling pathways

    Time frame: After completion of sequencing analyses; in vitro exposure for approximately 24 hours

    Candidate pathways identified by single-cell RNA sequencing will be tested in vitro using peripheral blood mononuclear cells collected at Day 0. Cells will be exposed to pathway activators or inhibitors, and the capacity to induce regulatory T cells will be measured by flow cytometry using markers including CD45, CD3, CD4, CD25 and Foxp3.

Study contacts

Contact information is provided by the study sponsor or research team.

Barbara SEITZ-POLSKI, MD, PhD, Professor

CONTACT

[email protected]

+33 4 92 03 40 11

Céline FERNANDEZ

CONTACT

[email protected]

+33 4 92 03 88 28

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nice

Other

Registry information

Official study title

A Study Using Single-cell RNA Sequencing (scRNA-seq) to Investigate the Mechanisms Underlying the Induction of Regulatory T Cells in Patients With Extramembranous Glomerulonephritis Treated With Rituximab

Acronym: TRANSCRIPT

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Sep 10, 2026
Registry last updated
Sep 10, 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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