IL-23/IL-12 Imbalance and T Lymphocyte Polarization in HIV Infection (INTESTIPAX)
ANRS RF002 Intestipax : Interleukin-23 (IL-23)/Interleukin-12 (IL-12) Imbalance and T Lymphocyte Polarization in HIV Infection
調査の概要
詳細な説明
Th17 lymphocytes fight bacterial and fungal intestinal infections. Under combined antiretroviral therapy, even if the plasma viral load is undetectable, hyperactivation can persist, inducing localized replication from reservoirs. In humans, Th17 lymphocyte differentiation and expansion depend on IL-23. The investigators were the first to uncover an imbalance in the respective production of IL-12 and IL-23 in response to Lipopolysaccharide (LPS) in HIV-1 infected patients. IL-23 and its receptor are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD) like Crohn's disease, where the mucosa is altered by Th17 cells, inducing bacterial product translocation. IBD can be efficiently treated by antibodies directed against Tumor Necrosis Factor-α (TNF-α) or, in current clinical trials, against the p40 chain which is shared by IL-12 and IL-23. Unfortunately, these antibodies inhibit also IL-12. IL-12 is crucial against mycobacteria, which are opportunistic in HIV-infected patients. Antibodies directed against the p19 chain of IL-23 would inhibit Th17 activation more specifically.
The investigators will collect blood and recto-colic biopsies from 15 healthy donors, 15 HIV-infected patients with a viral load higher than 5000 copies/ml and 15 patients with evolutive IBD, to establish a parallel between the two diseases.
The objectives of this project are to study if there is a correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to investigate the polarization, infection or depletion of intestinal Th17 ex vivo. Investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
If these correlations are validated, the investigators will propose anti-IL-23 neutralizing treatment to allow Th17 and intestinal integrity to come back into balance, and therefore to break the vicious cycle of immune system hyperactivation drawn by bacterial translocation.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
-
-
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Paris、フランス、75014
- Centre d'Investigation Clinique BT505, Hôpital Cochin
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
- Age higher than 18
- Able to give written consent
- Recto-colic biopsies prescribed for patient care
- Covered by French Health Insurance System (Social Security) (15 HIV patients with documented detectable HIV viral load in the past 6 months, 15 HIV negative patients with evolutive IBD, 15 HIV negative patients without evolutive IBD)
Exclusion Criteria:
- Absence of coverage by French Health insurance system (Social Security)
- Known progressive malignancy
- Indeterminate colitis
- Known autoimmune diseases other than IBD
- Current chemotherapy or radiotherapy
- Vulnerable populations (children, pregnant women, persons under legal guardianship, or deprived of freedom by judicial or administrative decision)
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 |
|---|---|
|
実験的：Patients with recto-colic biopsies prescribed
45 patients
|
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 |
時間枠 |
|---|---|
|
Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies.
時間枠：25 months
|
25 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies
時間枠：25 months
|
25 months
|
その他の成果指標
結果測定 |
時間枠 |
|---|---|
|
Multiple measures : HIV viral load levels in blood and intestinal biopsies
時間枠：25 months
|
25 months
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
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
- ANRS RF002 INTESTIPAX
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