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

NCT07811557 | Not Yet Recruiting

• 2 other identifiers: 25-AOI-01IDRCB 2025-A02468-41
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Membranous Nephropathy; Membranous Nephropathy - PLA2R Induced; Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from 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.

  Day 0 to Month 6

Secondary Outcomes (1)

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

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

Study Arms (1)

Rituximab-treated anti-PLA2R1-positive membranous nephropathy patients

OTHER

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

Interventions

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.

Rituximab-treated anti-PLA2R1-positive membranous nephropathy patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU de NICE

Nice, 06200, France

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranous; Nephrotic Syndrome

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; Nephrosis

Central Study Contacts

Barbara SEITZ-POLSKI, MD, PhD, Professor

CONTACT

+33 4 92 03 40 11; drc@chu-nice.fr

Céline FERNANDEZ

CONTACT

+33 4 92 03 88 28; fernandez.c3@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 10, 2026
• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

FR (1)