Crosstalk Between Mucosal-Associated Invariant T (MAIT) Cells and the Gut Microbiota and Mucosa in the Development of Type 1 Diabetes in Children
MAIT-DT1
2 other identifiers
observational
180
1 country
2
Brief Summary
To investigate in a prospective way changes in Mucosal-Associated Invariant T (MAIT) cells frequency, phenotype and function in link with the gut microbiota, gut integrity and the presence of Coxsackie virus B in two cohorts of pediatric patients: patients with a high genetic risk of type 1 diabetes and pediatric patients with recently diagnosed T1D by comparison with control subjects Tasks:
- 1.To measure blood MAIT cells frequency, phenotype and function in the three cohorts
- 2.To analyze gut microbiota and the presence of Coxsackie B enterovirus (CVB) and their impact on MAIT cell function
- 3.To evaluate gut integrity and analyze the gut mucosa
- 4.To integrate all the data obtained with T1D development and evolution
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Jan 2022
Longer than P75 for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2021
CompletedFirst Posted
Study publicly available on registry
September 23, 2021
CompletedStudy Start
First participant enrolled
January 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 11, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 14, 2027
April 13, 2026
April 1, 2026
4.6 years
June 8, 2021
April 8, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
blood MAIT cells frequency
percentage of MAIT cells in the peripheral blood
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
Secondary Outcomes (8)
MAIT cells membrane markers analysis
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
Cytokines production in the cytoplasm of the MAIT
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
MAIT cell ligands measurements
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
Presence of CVB in the stools
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
Blood immunoglobulins against CVB infection statu
Sample collected the day of enrollment (Control group and at risk patients) or up to 7 days after diagnosis and day of enrollment (recent onset group)
- +3 more secondary outcomes
Study Arms (4)
recent onset patients
patients with recently diagnosed type 1 diabetes
at risk patients
patients with a high genetic risk type 1 diabetes
control subjects
control patients (no risk of type 1 diabetes and no diagnosed type 1 diabetes)
control subjects for endoscopy
patients without type 1 diabetes requiring UGI endoscopy for any medical reason
Interventions
For FACS analysis, MAIT cells will be identified as CD3+ CD4- CD161high Vα7.2+ T cells. Surface markers will be analyzed to determine their activation status (CD25, CD69, CD44), their exhaustion (PD1, KLRG1, TIM3), their migration capacity (CCR6), and their proliferation and survival will be analyzed by Ki67 and BCL2 expression.
Cytokine production will be assessed after PMA-ionomycin activation, followed by intracytoplasmic staining with antibodies against IL-2, IFN-γ TNF-α, IL-2, IL-4, IL-10, IL-13, IL-17 and granzyme B. To determine the capacity of MAIT cells to response to TCR stimulation (exhaustion), in vitro stimulation will be performed in the presence of specific bacterial ligands. Activation marker expression will be analyzed by FACS and cytokines released in the supernatant by Cytometry based assay.
After an overnight fast, the patients will drink 50 ml solution of 5 g lactulose and 2 g mannitol. Urine will be collected during before and 5 hours later.
Duodenal biopsy collection and analysis. Biopsies will be analyzed by qPCR for the expression of key epithelial molecules such as the fucosyl transferase 2 (fut2), tight junction proteins (occludin, claudin4), antimicrobial peptides (Reg3, LL37) and mucus component (mucin 2). Immune cells function will also be assessed by q-PCR for key cytokines/molecules such as IL-23, IL-17, IL-22, Foxp3, IL-10, TGFb and CVB.
Serology against CVB and CVB specific-qPCR measurement in gut microbiota samples will be performed in all patients of the three cohorts, and analysis of the gut mucosa by qPCR and immunochemistry with anti-CVB VP1 protein mAb will be performed on a subset of patients.
Eligibility Criteria
Study population: patients recently diagnosed with type 1 diabetes and patients with a high risk of type 1 diabetes
You may qualify if:
- Recent onset group
- age \> 12 months and \< 15 years
- recently diagnosed type 1 diabetes according ISPAD criteria
- At risk subjects:
- age \> 12 months and \< 15 years
- siblings of type 1 diabetic patient
- HLA DR3 and DR4 positive
- Control subjects:
- age \> 12 months and \< 15 years
- no HLA associated with high risk type 1 diabetes
- no antibodies against pancreas antigenes
- Control subjects for UGI endoscopy:
- age \> 12 months and \< 15 years
- suspicion of coeliac disease or gastritis
You may not qualify if:
- For all groups:
- no health care insurance
- parents or tutors unable to sign the consent
- personal history of autoimmune disease and/or inflammatory disease except from T1D for RD and CE groups
- pregnant subjects
- medical contraindication of anesthetic topics
- For control subjects for UGI endoscopy control and Recent onset-endoscopy group:
- age below 8 years for Recent onset-endoscopy group
- age below 4 for UGI endoscopy control group
- cardiac or respiratory insufficiency, cardiac rhythm disorders, coagulation disease, patients treated with anticoagulant or antiaggregant drug
- history of allergy to anesthetic drug
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Hopital privé d'Antony
Antony, 92160, France
Hopital Necker enfants malades
Paris, 75015, France
Related Publications (2)
Rouxel O, Da Silva J, Beaudoin L, Nel I, Tard C, Cagninacci L, Kiaf B, Oshima M, Diedisheim M, Salou M, Corbett A, Rossjohn J, McCluskey J, Scharfmann R, Battaglia M, Polak M, Lantz O, Beltrand J, Lehuen A. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol. 2017 Dec;18(12):1321-1331. doi: 10.1038/ni.3854. Epub 2017 Oct 9.
PMID: 28991267BACKGROUNDRouland M, Beaudoin L, Rouxel O, Bertrand L, Cagninacci L, Saffarian A, Pedron T, Gueddouri D, Guilmeau S, Burnol AF, Rachdi L, Tazi A, Mouries J, Rescigno M, Vergnolle N, Sansonetti P, Christine Rogner U, Lehuen A. Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia. Gut. 2022 Feb;71(2):296-308. doi: 10.1136/gutjnl-2020-323664. Epub 2021 Feb 16.
PMID: 33593807BACKGROUND
Biospecimen
blood, stools, urines and gut mucosa samples
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2021
First Posted
September 23, 2021
Study Start
January 1, 2022
Primary Completion (Estimated)
August 11, 2026
Study Completion (Estimated)
August 14, 2027
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share