Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

NCT06427421 | Recruiting

• 2 other identifiers: APHP2306642024-A00696-41
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes (T1D) is caused by an autoimmune response leading to the destruction of pancreatic beta cells. The disease association with particular HLA class II alleles, particularly HLA-DQ8, indicates the implication of CD4 T cells in its aetiology. The hypothesis is therefore that T1D starts by the loss of tolerance in autoreactive CD4 T cells. This might result from alterations in conventional autoreactive CD4 T cells (Tcons), which drive disease, or autoreactive regulatory CD4 T cells expressing the transcription factor FOXP3 (Tregs), which normally maintain immune tolerance. The investigators expect that the characterization of HLA-DQ8-restricted Tcons and Tregs in recent onset HLA-DQ8+ T1D patients shall shed light on the molecular mechanisms underpinning T1D development. This knowledge will guide the development of novel cell therapies harnessing the power of genetically engineered Tregs expressing the relevant antigen receptor to restore immune homeostasis upon cell transfer. The ultimate goal is to reach a curative effect

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Regulatory T cells; Pathophysiology of T1DM

Outcome Measures

Primary Outcomes (1)

• Frequency and phenotype of Tregs

  study the frequency and phenotype of insulin-specific autoreactive Tregs lymphocytes among CD4+ T lymphocytes in children with T1DM and compare these values with those of controls. These parameters will be analyzed by flow cytometry using immune cells from blood samples taken from the T1DM and control groups.

  Within 4 weeks of T1DM diagnosis

Secondary Outcomes (5)

• HLA testing

  Within 4 weeks of T1DM diagnosis

• Isolate insulin-specific Tregs and Teffs cells

  Within 4 weeks of T1DM diagnosis

• Treg and Teffs transcriptome

  Within 4 weeks of T1DM diagnosis

• Full TCR repertoire of Tregs and Teffs

  Within 4 weeks of T1DM diagnosis

• Machine learning analysis

  Within 4 weeks of T1DM diagnosis

Study Arms (2)

Newly diagnosed T1DM group

OTHER

children aged 2 to under 18 on the day of inclusion, with a recent diagnosis of type 1 diabetes

Biological: Frequency of Treg and Teffs; Biological: Phenotype of Treg and Teffs; Biological: RNA seq analysis; Biological: HLA typing; Biological: beta-cell autoantibody dosage

Control group

OTHER

children aged 2 to under 18 on the day of inclusion, with no history of type 1 diabetes

Biological: Frequency of Treg and Teffs; Biological: Phenotype of Treg and Teffs; Biological: RNA seq analysis; Biological: HLA typing; Biological: beta-cell autoantibody dosage; Biological: Glycated haemoglobin (HbA1C) dosage; Biological: blood glucose dosage; Biological: C-peptide dosage

Interventions

Frequency of Treg and Teffs BIOLOGICAL

additionnal blood sampling at inclusion

Control group; Newly diagnosed T1DM group

Phenotype of Treg and Teffs BIOLOGICAL

additionnal blood sampling at inclusion

Control group; Newly diagnosed T1DM group

RNA seq analysis BIOLOGICAL

additionnal blood sampling at inclusion

Control group; Newly diagnosed T1DM group

HLA typing BIOLOGICAL

additionnal blood sampling at inclusion

Control group; Newly diagnosed T1DM group

beta-cell autoantibody dosage BIOLOGICAL

additionnal blood sampling at inclusion

Control group; Newly diagnosed T1DM group

Glycated haemoglobin (HbA1C) dosage BIOLOGICAL

additionnal blood sampling at inclusion

Control group

blood glucose dosage BIOLOGICAL

additionnal blood sampling at inclusion

Control group

C-peptide dosage BIOLOGICAL

additionnal blood sampling at inclusion

Control group

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Newly diagnosed T1DM group:
• Weight ≥ 12 kg;
• Newly diagnosed T1DM, diagnosis defined according to International Society of Pediatric and Adolescent Diabetes (ISPAD) criteria by: hyperglycemia \> 2g/L and/or ketonemia and/or polyuro-polydipsia and/or weight loss ;
• Absence of other associated inflammatory or autoimmune diseases;
• Affiliation with a health insurance scheme or beneficiary (excluding AME);
• Written consent of parental guardians;
• Ability to understand and read French.
• Control group :
• Weight ≥ 12 kg;
• No personal history of T1DM;
• Affiliation with a health insurance scheme or entitled person (excluding AME);
• Written consent from parental guardians;
• Ability to understand and read French.

You may not qualify if:

• Newly diagnosed T1DM group:
• Use of oral or intravenous corticosteriods in the month prior to blood sampling
• Contraindication to the use of anaesthetic cream for blood sampling.
• Control group :
• History of autoimmune or inflammatory disease
• Use of oral or intravenous corticosteriods in the month prior to blood sampling
• Contraindication to the use of anaesthetic cream for blood sampling

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hôpital Necker Enfants Malades

Paris, 75015, France

RECRUITING

Related Publications (18)

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Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Single-Cell Gene Expression Analysis; Histocompatibility Testing; Glycated Hemoglobin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Single-Cell Analysis; Cytological Techniques; Investigative Techniques; Gene Expression Profiling; Genetic Techniques; Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Immunologic Techniques; Glycated Serum Proteins; Glycated Proteins; Glycation End Products, Advanced; Glycoconjugates; Carbohydrates; Glycoproteins; Hemoglobins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globins; Hemeproteins; Toxins, Biological; Biological Factors

Study Officials

• Simon FILATREAU, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY DIRECTOR

Central Study Contacts

Jacques BELTRAND, MD, PhD

CONTACT

+33 1 40 61 53 20; jacques.beltrand@aphp.fr

Sarah BOUCHARD

CONTACT

+ 33 1 42 19 28 79; sarah.bouchard@aphp.fr

Study Design

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

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 23, 2024
• Study Start: May 6, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)