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.
調査の概要
状態
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Barbara SEITZ-POLSKI, MD, PhD, Professor
- 電話番号：+33 4 92 03 40 11
- メール：drc@chu-nice.fr
研究連絡先のバックアップ
- 名前：Céline FERNANDEZ
- 電話番号：+33 4 92 03 88 28
- メール：fernandez.c3@chu-nice.fr
研究場所
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Nice、フランス、06200
- Chu De Nice
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コンタクト：
- Céline FERNANDEZ
- 電話番号：+33 4 92 03 88 28
- メール：fernandez.c3@chu-nice.fr
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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他の：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in regulatory T-cell induction and rituximab-modulated immune signaling pathways from Day 0 to Month 6
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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In vitro induction of regulatory T cells by modulators of rituximab-associated signaling pathways
時間枠：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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協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 25-AOI-01
- IDRCB 2025-A02468-41 (その他の識別子：ANSM)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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