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Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients (NEOMAIT)

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ClinicalTrials.gov Identifier: NCT02403089
Recruitment Status : Completed
First Posted : March 31, 2015
Last Update Posted : March 2, 2018
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Institut National de la Recherche Agronomique
Institut Curie
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The objective of this study is 1/ to determine the rate and kinetics of MAIT cell expansion and maturation in neonates in relation with gestational age, and in HSCT recipient children in relation with the source of donor stem cells, 2/ to correlate gut microbiota diversity and function with MAIT cell maturation and function in neonates and HSCT recipients; and 3/ to link MAIT cells and gut microbiota composition with microbial infections and severe intestinal inflammatory events in term and preterm neonates, and in HSCT recipients

Condition or disease Intervention/treatment
Term and Preterm Neonates (24-41 Weeks Gestational Age) Hematopoietic Stem Cell Transplant Recipient Children Other: Tubes fund recovery blood count Other: the rest of the blood test and stool sample

Detailed Description:

The mucosa-associated invariant T (MAIT) cells are innate-like T cells with restricted T cell receptor (TCR) usage, which are preferentially localized in mucosal tissues and respond to microbial infection by rapidly producing cytokines and cytotoxic effectors. They recognize the non-classical related molecule (MR1). MAIT cells react against a newly identified class of antigens presented by MR1: Riboflavin (Rib) precursors, which are found in most bacteria and yeasts. Currently, very little is known about the ontogeny of MAIT cells in the human, because of the difficulty to follow longitudinally their development. Cross-sectional studies have identified only the initial (cord blood) and final (adult subjects) steps of human MAIT cell maturation program. Moreover, there are no data on relationships between human MAIT cell expansion and maturation, and gut microbiota development. Given the potential importance of MAIT cells in protection from microbial infections at epithelial surfaces, we will investigate the maturation dynamics of MAIT cells in relation with gut microbiota diversity and function in two clinical settings characterized by a high predisposition to severe microbial infections before the establishment of protective adaptive immunity, namely i/ the neonatal period and ii/ the early immune reconstitution period following allogeneic hematopoietic stem cell transplantation (HSCT) in children. Our study will combine multiparametric phenotypic and functional characterization of MAIT cells with the use of new molecular microbiota analytic methodology (high throughput sequencing, metagenomics, Rib microbiology) to determine how the presence or functionality of MAIT cells is influenced by the gut microbiota.

Our consortium is composed of three independent research teams, experts in innate immunity, microbial ecology and MAIT cell biology, three independent clinical teams providing exceptional resources to patient samples, and one team providing expertise for methodology and statistical analysis. Their synergistic interaction will offer the various complementary expertise that is necessary for this project.

This project will decipher how MAIT cell numbers or functions are influenced by the gut microbiota composition, and reciprocally, how MAIT cells regulate or control expansion of gut microbiota components competing with opportunistic or pathogenic bacteria or responsible for infections. Ultimately, this study will determine how and when gut microbiota and MAIT cell interactions are involved in the control of severe infectious or intestinal inflammatory events in high risk infants, an indispensable step to design predictive biomarkers and ultimately propose new therapeutic options.

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Study Type : Observational
Actual Enrollment : 300 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients
Actual Study Start Date : March 2015
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018

Group/Cohort Intervention/treatment
neonates
neonates 24-41 weeks gestational age
Other: Tubes fund recovery blood count
Tubes fund recovery of blood counts among newborns

children
hematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor)
Other: the rest of the blood test and stool sample
blood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination.




Primary Outcome Measures :
  1. MAIT cell numbering neonates after birth [ Time Frame: to 60days ]
    Absolute number, percentage and phenotype of MAIT cells by flow cytometry in the circulating blood after birth according to gestational age and / or maternal-fetal infections (IMF), or after allogeneic HSCT according to the origin of HSCs.


Secondary Outcome Measures :
  1. Absolute number of MAIT [ Time Frame: to 60days ]
    Absolute number and percentage of MAIT among mothers of infants on the day of delivery and in geno-identical donors before transplantation.

  2. Absolute number of other immune cell populations [ Time Frame: to 60 days ]
    Absolute number and percentage of other immune cell populations by flow cytometry on the same blood samples.


Biospecimen Retention:   Samples Without DNA

funds tubes samples taken as part of routine care for newborns and in allograft recipients children will be recovered. Mononuclear cells from cord blood will be isolated and stored in liquid nitrogen in the laboratory of Immunology before achieving functional tests.

• Rectal swabs and gastric aspirates aliquots made as part of routine care for newborns, and rectal swabs made as part of routine care in HSCT allograft recipients, will be stored at -80 ° C in the laboratory of Immunology.



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
newborns hospitalized in the Neonatal Intensive Care Unit of the Hospital Robert Debré and grafted children hospitalized in the Hematology-Immunology Pediatric Service of the Hospital Robert Debré
Criteria

Inclusion Criteria:

  • neonates 24-41 weeks gestational age
  • hematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor)

Exclusion Criteria:

  • neonates : chromosomal abnormalities detected before birth
  • source of HSCT: phenol-identical donors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02403089


Locations
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France
Hôpital Robert Debré
Paris, France, 75019
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Institut National de la Recherche Agronomique
Institut Curie
Investigators
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Principal Investigator: Biran Valérie, PHD Assistance Publique - Hôpitaux de Paris
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02403089    
Other Study ID Numbers: NI14006
First Posted: March 31, 2015    Key Record Dates
Last Update Posted: March 2, 2018
Last Verified: February 2018
Keywords provided by Assistance Publique - Hôpitaux de Paris:
MAIT (Mucosal-Associated Invariant T) cells
Gut microbiota
Preterm birth
Hematopoietic stem cell transplantation
Microbial infections
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications