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 (TRANSCRIPT)
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
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.
Studie Overzicht
Toestand
Studietype
Inschrijving (Geschat)
Fase
- Niet toepasbaar
Contacten en locaties
Studiecontact
- Naam: Barbara SEITZ-POLSKI, MD, PhD, Professor
- Telefoonnummer: +33 4 92 03 40 11
- E-mail: drc@chu-nice.fr
Studie Contact Back-up
- Naam: Céline FERNANDEZ
- Telefoonnummer: +33 4 92 03 88 28
- E-mail: fernandez.c3@chu-nice.fr
Studie Locaties
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Nice, Frankrijk, 06200
- Chu De Nice
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Contact:
- Céline FERNANDEZ
- Telefoonnummer: +33 4 92 03 88 28
- E-mail: fernandez.c3@chu-nice.fr
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Fundamentele wetenschap
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Ander: Rituximab-treated anti-PLA2R1-positive membranous nephropathy patients
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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.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6
Tijdsspanne: Day 0 to Month 6
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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.
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Day 0 to Month 6
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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In vitro induction of regulatory T cells by modulators of rituximab-associated signaling pathways
Tijdsspanne: After completion of sequencing analyses; in vitro exposure for approximately 24 hours
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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.
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After completion of sequencing analyses; in vitro exposure for approximately 24 hours
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Medewerkers en onderzoekers
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Urogenitale ziekten
- Mannelijke urogenitale ziekten
- Nier Ziekten
- Urologische ziekten
- Vrouwelijke urogenitale ziekten
- Vrouwelijke urogenitale ziekten en zwangerschapscomplicaties
- Auto-immuunziekten
- Ziekten van het immuunsysteem
- Glomerulonefritis
- Nefritis
- Nefrose
- Nefrotisch syndroom
- Glomerulonefritis, membraanachtig
Andere studie-ID-nummers
- 25-AOI-01
- IDRCB 2025-A02468-41 (Andere identificatie: ANSM)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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