Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals (CARegT1D)

NCT06427421 NA RECRUITING

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

Details

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	NA
Status	RECRUITING
Enrolment	80
Start date	2025-05-06
Completion	2027-05

Conditions

• Type 1 Diabetes

Interventions

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

Primary outcomes

• Frequency and phenotype of Tregs — Within 4 weeks of T1DM diagnosis
  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.

Countries

France