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

Immune correlates of disease progression, regulation and therapeutic intervention (#42)

Bart Roep 1
  1. Leiden University Medical Center, Leiden, Netherlands
Since type 1 diabetes results from a T-cell mediated beta-cell destruction, it is conceivable that monitoring islet autoreactive T-cells offers opportunities to trail pathogenic processes. Indeed, circulating islet autoreactive T-cells can be measured  reproducibly. These T-cells can be isolated from diabetic pancreata, their specificities are matched with those detected in human insulitic lesions in situ and cultured clones isolated from type 1 diabetic patients can recapitulate insulitis in humanized mouse models, supporting their potential diabetogenicity. Perhaps more importantly, their frequencies in blood predict clinical outcome of stem cell therapy and islet transplantation and changes in their frequencies associate with relapsing disease, while the autoimmune signature distinguishes different immunotherapeutic strategies, pointing to the possibility that monitoring these T-cells may stage patients for customized therapy (personalized medicine) and guide and optimize immunotherapy. Yet, the difficulty to identify and monitor tissue specific regulatory Tcells (aTregs) poses a critical gap, while I contend that the range of islet epitopes currently tested as candidate biomarkers in type 1 diabetes need not be the most rewarding and relevant spectrum to use as immune correlates of disease progression, remission and therapeutic intercention. For instance, many candidate epitopes have been selected on basis of xenogeneic models and high binding HLA affinity whereas auto-epitopes often possess low binding affinities, the islet peptide repertoires of the most strongly disease predisposing HLA-DQcis and -trans molecules have not yet been defined in great detail and it is conceivable that posttranslationally modified autoantigens, rather than their native counterpart, prove to be most relevant to disease. The current knowledge and challenges to discover, validate and apply immune correlates of disease progression, immune regulation and therapeutic intervention will be discussed.