Profiling of Original Cellular and Humoral Biomarkers of Type 1 Diabetes

Profiling of Original Cellular and Humoral Biomarkers of Type 1 Diabetes

The "Lymphoscreen" study aims to characterize precisely (phenotypes/cytokines/functions) CD8+ T cell responses in type 1 Diabetes to identify biomarkers of the disease. Such markers are needed for refine type 1 Diabetes diagnosis/prognostic, and to design new therapeutic approaches targeting autoreactive CD8+ T cells. An original approach using DNA immunization of humanized mice allowed us to identify relevant CD8 epitopes derived from GAD65 and IA-2 beta cell autoantigens. The aims are: (i) identifying exhaustively epitopes recognized by autoreactive CD8+ T lymphocytes in type 1 Diabetes and following islet or pancreas graft in humans; (ii) identifying pathogenic CD8+ T cell patterns or profiles related to type 1 Diabetes pathogenesis and evolution; (iii) correlating CD8+ autoreactive T cell responses and autoantibody responses to new cellular (such as CD4+ T cells or peripheral cell miRNA) or humoral markers of the disease (such as serum miRNA).

Inclusion criteria:

• at least, 50 patients with "recent" type 1 diabetes,
• 30 patients with long-term type 1 diabetes,
• 10 patients with Latent Autoimmune Diabetes,
• 10 subjects with a risk for diabetes,
• 20 type 1 diabetic patients with pancreatic graft or Langerhans islet graft.
• 50 healthy subjects paired to HLA class I and to the age

Those subjects have to respect the following criteria :

• Age from 7 to 70 -Caucasian
• Affiliated to a national insurance scheme
• Written informed consent obtained For children, written informed consent is required from the two parents.

Non-inclusion criteria :

• Age strictly inferior to 7 or strictly superior to 70 years old
• Pregnancy
• Secondary diabetes
• No written informed consent