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Master Thesis

Quantification des lymphocytes T autoréactifs circulants au cours du diabète insulino-dépendant

Abstract : The ability to reliably detect autoreactive T cells in type 1 diabetes still constitutes a major challenge. In fact, relevant biological markers are still crucially needed in order to better assess immunotherapies, but also to improve prediction of type 1 diabetes in patients flagged as being at risk for the disease. Most existing studies in the field have been conducted so far in the adult population on the basis of the knowledge of HLA-restricted immunodominant epitopes targeted by T cells. The ELISPOT assay evaluated in this study was performed in a paediatric population, at the time of type 1 diabetes diagnosis. Autoantigens used for autoreactive T cell enumeration awere overlapping peptide pools (commercial pools for GAD, IA2 and insulin; custom peptide library for ZnT8), which made it possible to test all included children, independently of HLA restriction. Low frequencies of GAD-, IA2- and insulin-specific T cells were identified, as previously reported by others. By contrast, both frequencies of ZnT8-specific T cells and ZnT8 antibody titer were clearly lower than what has been described, which could be due to a statistical bias, linked to the small size of our sample. Using overlapping peptide pools, rather than HLA restricted epitopes, does not seem to improve the detection of autoreactive T cells. The frequency of these autoreactive T cells appears low, as well as the number of positive patients. The ELISPOT assay, which is basically technically mature, could however be improved based on the recent identification of immunogenic hybrid fusion peptides both in the NOD mouse model of type 1 diabetes and in diabetic patients.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03623267
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Submitted on : Friday, April 1, 2022 - 2:32:01 PM
Last modification on : Thursday, April 7, 2022 - 3:09:33 AM

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Baptiste Moreira. Quantification des lymphocytes T autoréactifs circulants au cours du diabète insulino-dépendant. Médecine humaine et pathologie. 2017. ⟨dumas-03623267⟩

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