Unlikeother autoimmune diseases, in coeliac disease the trigger factor is uniquely identifiableas gluten.
The main causative agents of the disease are dominant HLA andautoantibodies against Thyroglobulin which was detected in more than 95% of individualsin coeliac disease4.Thepathogenesis of coeliac disease is proposed to be by different pathways whichleads to destruction of epithelium and villous atrophy caused by gluten whichis the storage protein found in wheat, barley and rye. Gliadin is aglycoprotein extract from gluten that causes the overexpression of IL-5 in theintestine that is considered to be toxic to enterocyte. It also upregulates theMIC-A stress molecule on the surface of enterocytes and NKG2D receptor on theinfiltrating intraepithelial lymphocytes thus promoting a lymphocyte-mediatedcytotoxic response towards the enterocytes which depends on IL-15.TG has apivotal role in the pathogenesis of coeliac disease, gliadin is ingested intoenzyme crosslinks causing specific deamidation of glutamine into glutamic acidwithin the gliadin peptides. This deamidation process makes the gliadinpeptides more open to the gliadin -reactive CD-4 T cells in context of MHC-DQ2 moleculethus increasing immunogenicity. Gliadin is believed to be less immunogenic andmight not stimulate T cells efficiently without TG.
Gliadin is very richproline residues which is resistant to digestion in the intestine and bindswith DQ2 molecules. The absorption of these large intact peptides of gliadin isbelieved to initiate immunogenic response 5.TG playsan important role in the molecular level as in involved in deamidation ofgliadin and crosslinking, but there is very little evidence to support thetheory that TG has an immunologic role.
The TG autoantibodies are believed toform by antigen presenting cells targeting the toxic gliadin peptides taking upTG-gliadin complexes resulting in immune reaction against gliadin and TG. Thegeneration of gliadin-reactive T cells are a combined effect of adaptive andinnate immune system, leading to a cytotoxic response and antibody formation5.hh