IL-23/IL-12 Imbalance and T Lymphocyte Polarization in HIV Infection
- Conditions
- HIV Reservoirs
- Interventions
- Other: Blood sample and recto-colic biopsies
- Registration Number
- NCT01942655
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- Brief Summary
Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+ T cell loss and prognosis. The objectives of this project are to investigate the correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to study the polarization, infection or depletion of intestinal Th17 ex vivo. The investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Not provided
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Patients with recto-colic biopsies prescribed Blood sample and recto-colic biopsies 45 patients
- Primary Outcome Measures
Name Time Method Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies. 25 months
- Secondary Outcome Measures
Name Time Method Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies 25 months
Trial Locations
- Locations (1)
Centre d'Investigation Clinique BT505, Hôpital Cochin
🇫🇷Paris, France