REGulatory T Cells in Autism Induced by Maternal Immune Activation

NCT06169111 | Unknown

• 2 other identifiers: APHP230622IDRCB: 2023-A01329-36
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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

Autism Spectrum Disorder

Keywords

neurodevelopemental disorders; immunology; regulatory T lymphocytes

Outcome Measures

Primary Outcomes (1)

• To compare Tregs count (% CD4+) and Th17 count (% CD3+) and their ratio in ASD patients with and without MIA

  Evaluation of the Tregs count/Th17 balance in ASD patients with and without MIA

  24 months

Study Arms (2)

Autism Spectrum Disorders (ASD) patients with Maternal Immune Activation (MIA)

EXPERIMENTAL

Biological: REGulatory T cells in Autism induced by maternal Immune activation

Autism Spectrum Disorders (ASD) patients without Maternal Immune Activation (MIA)

ACTIVE COMPARATOR

Biological: REGulatory T cells in Autism induced by maternal Immune activation

Interventions

REGulatory T cells in Autism induced by maternal Immune activation BIOLOGICAL

REGulatory T cells in Autism induced by maternal Immune activation

Autism Spectrum Disorders (ASD) patients with Maternal Immune Activation (MIA); Autism Spectrum Disorders (ASD) patients without Maternal Immune Activation (MIA)

Eligibility Criteria

• Age: 3 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Patients with positive diagnosis of ASD according to DSM-5 (APA, 2015);
• Informed consent signed by both parents and oral agreement in principle given by the subject;
• Patients affiliated to a social security system

You may not qualify if:

• Patients with severe/profound intellectual disability;
• Uncontrolled epileptic seizures;
• Maternal infection during pregnancy with a pathogen with a known direct cerebral cytotoxic effect (CMV);

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Robert Debré Hospital

Paris, 75019, France

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Richard DELORME, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard DELORME, MD, PhD

CONTACT

+331.40.03.41.30; richard.delorme@aphp.fr

Pierre ELLUL

CONTACT

+331.40.03.41.31; pierre.ellul@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 13, 2023
• Study Start: January 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: December 13, 2023

Record last verified: 2023-11

Locations

FR (1)