The collaborative project DIAPREPP specifically addresses the call FP7 Cooperation Work Programme: Health-2007-2.4.3-1 Early processes in the pathogenesis of type 1 diabetes and strategies for early prevention.


The earliest currently identifiable process in the pathogenesis of type 1 diabetes (T1D) is the development of autoimmunity to islet beta cells in the form of autoantibodies. Hindering attempts to prevent autoimmune T1D, the aetiology and pathogenesis of the islet auto-immunization, including whether it is preceded by metabolic abnormalities and cell-mediated autoimmunity, is still poorly understood.

To overcome this, DIAPREPP will focus on the early auto-immunization against islet antigens, in particular to disclose events preceding current autoantibody markers. The concept is that events prior to auto-immunization govern the likelihood and 'signature' of immunization, which in turn determines progression to disease. The overall objective is to determine mechanisms of islet autoantigen immunization. In a truly collaborative manner, and through five workpackages plus three dedicated to dissemination, training, and management, DIAPREPP will

1. provide a unique set of clinical material that includes a case-control cohort representative of the world's largest studies of pre-T1D, with follow-up and samples from birth, and pancreatic islets and lymph nodes from patients;

2. investigate the effects of environmental exposure to infections on islet cells and immune cells;

3. perform extensive metabolomic analysis of pre-autoimmune samples and in relevant animal models to test mechanistic hypotheses of auto-immunization;

4. carry out detailed analyses of early autoimmune responses with a special focus on autoreactive CD8+ T cells;

5. apply findings to ongoing prevention studies.

 

The expected impact of DIAPREPP is new fundamental knowledge regarding how

1. immunization against islet autoantigens can occur

2. signs of self-immunization can be exploited for prediction and monitoring of disease

3. the immunization or its progression to islet beta cell destruction and T1D development can be prevented.

 


Coordinator - Ezio Bonifacio
ezio.bonifacio@crt-dresden.de