Mechanisms of Pathogenesis in Celiac Disease and Non-Celiac Gluten Sensitivity

Celiac disease (CD) has in recent years become understood as a disease in which the importance of complete digestion of gliadin is essential for safe management of patients. Lately, the use of enzyme therapy for treatment of CD has gained wider acceptance as an adjunct to the gluten-free diet. A closer examination of Non-Celiac Gluten Sensitivity (NCGS) is warranted to determine if enzyme supplementation could be beneficial for individuals with this condition. Incomplete digestion of gluten produces toxic and/or immunologically active peptides which are implicated in both CD and in NCGS. These peptides are from a region close to the N-terminus of A-gliadin and contain serine or tyrosine residues. NCGS is caused by certain serine-containing peptides in A-gliadin and particularly those near the N-terminus. Peptide 11-19 is the most active of these peptides in vitro but may not be involved in cell-mediated immune reactions in CD. These reactions are related to tyrosine-containing peptides. Further along the chain is peptide 75-86, the most tissue damaging of the A-gliadin peptides in CD patients. This peptide is a tyrosine-containing peptide where damage caused to mucosal tissue is greater in CD than in NCGS. Hence, although CD and NCGS are both caused by gluten, the pathogenesis of the diseases has different mechanisms. However, both serine-containing and tyrosine-containing peptides are attacked by caricain, the protective enzyme in GluteGuard, thus rendering both types of toxic peptides harmless to the intestinal mucosa of susceptible individuals. Just as has been seen with Dermatitis Herpetiformis (DH), gluten is becoming a focus for several conditions when the neurological effects of gluten need to be considered.