Marie Curie Research Training Network
TRACKS
Transglutaminases: role in pathogenesis, diagnosis and therapy (TRACKS)
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Objective 3 : Role of TGase in Coeliac Disease
It has been demonstrated that TG2 and gliadin can form complexes. As a consequence TG2 specific B cells may internalise these complexes via membrane immunoglobulin and thereby efficiently present gluten peptides bound to HLA DQ2 or -DQ8 to gluten reactive T helper cells. The gluten reactive T cells may in this way provide the necessary T cell help.
The following will be undertaken:
- Analysis of the propensity of TG2 to mediate deamidation vs transamidation.
- Analysis of where the deamidation of gluten peptides by TG2 takes place in celiac intestinal mucosa. Specifically the expression of TG2 by antigen presenting cells like monocytes and dendritic cells will be studied and it will be investigated whether surface TG2 on such cells can be endocytosed together with gluten peptides.
- To confirm whether celiac disease specific IgA class patient autoantibodies have a role in CD pathogenesis.
- To confirm whether specific TG2 inhibitors and/or TG2 antibodies (objectives 4 and 5) prevents mucosal damage when organ cultures obtained from treated celiac disease patients are treated with peptic-tryptic digests of gliadin or with disease inducing gliadin peptides.
- Evaluation and development of a simple more reliable non-invasive screening test for CD (objective 6). Partner No 3 has filed a patent (Method and means for detecting gluten-induced disease, PCT/F102/00340, No. WO02/086509) based on a whole blood test which can be further developed to provide a rapid and cheap point-of-care-test.
