Celiac Disease Pathogenesis

The triggers for celiac disease are specific immunogenic peptides that are present only and exclusively in the dietary gluten proteins, from wheat and similar structural cereals such as rye and barley. These peptides are resistant to digestion by gastric and pancreatic enzymes and fi nd their way into the lamina propria of the small bowel, presumably after some changes occur in the intercellular tight junctions with an increase in the intestinal permeability. One such peptide is a 33-amino acid sequence, which is a potent activator of specific T-cell lines from patients with CD.

The subsequent infiltration by CD4 (+) T lymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium, are a hallmark of active CD. The recognition of HLA-bound gluten peptides by T cells, leads to their activation and clonal expansion of B cells that produce antibodies. Other cytokines released by activated CD4 T cells that involve the adaptive immune response, promote various inflammatory mechanisms and produce the intestinal lesion. Less information is available on the activation and mode of action of intraepithelial T cells, which are mediated by the innate immune system

. The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage[16]. Tissue transglutaminase 2 (tTG), plays an important role in the immune response and is present in several tissues in the body.

The cross-linking activity of tTG is involved in several functions, such as wound healing, formation of cell envelopes in apoptosis and stabilization of the extra-cellular matrix. In addition, this enzyme can deaminate glutamine residues.

Glutamine-rich gluten peptides are, therefore, excellent substrates for tTG. The resulting deaminated and thus, negatively-charged peptides, have much higher affinity for the HLA-DQ2 and DQ8 molecules, and have a key step in the immune response in CD[17].

 In summary, we must say that celiac disease is a complex disorder that results from an interplay of several genetic, immunological and environmental factors, with many aspects for which the final pathogenetic mechanisms remains to be solved.