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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Rituximab-treated anti-PLA2R1-positive membranous nephropathy patients
干预措施: Peripheral blood immune-cell profiling by single-cell RNA sequencing and in vitro pathway modulation assays (Other)
结局指标
主要结局
Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6
时间窗: 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.
次要结局
- 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)