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REGulatory T Cells in Autism Induced by Maternal Immune Activation

NCT06169111 · Status: NOT_YET_RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 70

Last updated 2023-12-13

No results posted yet for this study

Summary

Autism Spectrum Disorders (ASD) represent a heterogeneous clinical entity of neurodevelopmental disorders affecting around 1% of the general population (Lord et al. 2020). There is currently no curative treatment for patients with ASD, and management does not take into account the existence of specific patient subgroups. Beyond genetic factors (Delorme et al. 2013), environmental factors play a fundamental role in the determinism of ASD. Among them, maternal immune activation (MIA) during pregnancy is a recognized risk factor for ASD in children (Estes and McAllister 2016). Our team has helped to demonstrate that MIA induced by infections or autoimmune pathologies in the mother during pregnancy (particularly at the end of the 1st trimester/beginning of the 2nd trimester) significantly increases the risk of ASD in the offspring (Antoun et al. 2021). Mechanistically, MIA leads to a deregulation of the regulatory T lymphocyte (Tregs)/Th17 balance (in the direction of a decrease in anti-inflammatory Tregs and an increase in pro-inflammatory Th17) in the mother but also, via epigenetic mechanisms, in the fetus (Lim et al. 2021). Our team have recently demonstrated the same Tregs/Th17 deregulation profile in ASD patients (Ellul et al. 2021). This disruption of the Tregs/Th17 balance is responsible for disrupting fetal brain development via IL-17 receptors present on fetal neurons (Choi et al. 2016). Importantly, these socio-communicative and morphological abnormalities appear, in specific animal models, to be reversible upon restoration of the Tregs/Th17 balance (Z. Xu et al. 2021; Choi et al. 2016). While data on the involvement of IL-17 are becoming better known, the role of Tregs in this model has been surprisingly little studied.Our overall aim is therefore, in humans and mice, to determine the role of Tregs and IL-17-producing lymphocytes in the development and maintenance of autistic symptoms triggered by MIA.

Our specific objectives in humans will be to use an existing cohort (EXPECT) of ASD patients to compare those with and without a history of MIA using a standardized clinical evaluation (including overall autism severity, language and motor development, adaptive behaviors,comorbidities), a systems immunology assessment (combining deep immunophenotyping by flow cytometry, cytokine measurements - simultaneous Luminex assay of 50 pro-inflammatory cytokines associated with Th1/Th2/Th17/Treg responses) and a targeted quantitative metabolomics analysis of the tryptophan pathway.

Conditions

Interventions

BIOLOGICAL

REGulatory T cells in Autism induced by maternal Immune activation

REGulatory T cells in Autism induced by maternal Immune activation

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Principal Investigators

  • Richard DELORME, MD, PhD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
3 Years
Max Age
15 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2024-01-01
Primary Completion
2025-01-01
Completion
2026-01-01

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06169111 on ClinicalTrials.gov