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.
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Barbara SEITZ-POLSKI, MD, PhD, Professor
- 전화번호: +33 4 92 03 40 11
- 이메일: drc@chu-nice.fr
연구 연락처 백업
- 이름: Céline FERNANDEZ
- 전화번호: +33 4 92 03 88 28
- 이메일: fernandez.c3@chu-nice.fr
연구 장소
-
-
-
Nice, 프랑스, 06200
- Chu De Nice
-
연락하다:
- Céline FERNANDEZ
- 전화번호: +33 4 92 03 88 28
- 이메일: fernandez.c3@chu-nice.fr
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
다른: Rituximab-treated anti-PLA2R1-positive membranous nephropathy patients
|
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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
In vitro induction of regulatory T cells by modulators of rituximab-associated signaling pathways
기간: 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.
|
After completion of sequencing analyses; in vitro exposure for approximately 24 hours
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 25-AOI-01
- IDRCB 2025-A02468-41 (기타 식별자: ANSM)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .