Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

The prediabetic period – seroconversion and progression as distinct stages with multiple determinants. (#40)

Ezio Bonifacio 1
  1. DFG-Center for Regenerative Therapies Dresden, TU Dresden, Dresden, Germany

Autoimmunity to islet beta cells is marked by the appearance of islet autoantibodies and occurs prior to diabetes onset. This seroconversion is pronounced at around 1 year of age, is often against insulin, and is associated with >80% risk for the development of diabetes once it spreads to other antigens such as GAD65, IA-2, or ZnT8. Moreover, we show that islet autoantibody seroconversion is synchronous with CD4+ T cell activation. Factors which associate with seroconversion include HLA class II and PTPN22 genotypes, type 1 interferon transcriptome signatures and disrupted microbiome networks, whereas maternal type 1 diabetes is associated with a relative protection of seroconversion. A number of genes including CD25, IL-2, INS, and IFIH1 influence the rate of progression to diabetes after seroconversion. Moreover, we find that an intrinsic phenotype of autoreactive T cell responsiveness to autoantigen in the preseroconversion period associates with the likelihood of disease progression.  These findings identify numerous pathways to islet autoimmunity and diabetes and as a consequence open opportunities for intervention.