The importance of alternative or adjunct treatments to the gluten-free diet in celiac disease is now being recognized. This paper discusses the scientific principles behind the use of caricain for enzyme therapy. Objective: To review the structures of the toxic peptides in A-gliadin that relate to those found by other workers insofar as having key sequences of amino acids or motifs which relate to toxicity, especially in regard to difficulty of digestion or immunogenicity. Methods: Structures of synthetic A-gliadin peptides shown to be toxic in the fetal chick assay were examined before and after digestion with duodenal mucosa from patients in long remission. Synthetic peptides corresponding to the undigested residues were also assayed and the key amino acid sequences compared in order to determine if they could be related to direct toxicity and immunogenicity of the peptides. Results: The results showed that the smallest toxic peptides from celiac mucosal digestion were octa-peptides and that they were obtained in greater yield than similar products from normal digestion. One of those peptides corresponded to residues 12-19 of A-gliadin and contained the key motifs PSQQ and QQQP of De Ritis et al. , whilst the other corresponded to residues 72-79 and contained the key motif PYPQ (extending to PYPQPQ), observed by other workers, especially those who have been investigating immunological activity over the past two decades. Conclusions: The presence of key motifs in undigested residues from celiac mucosal digestion and the greater prevalence of these residues compared with residues from normal digestion justifies our work on enzyme therapy. These studies have also indicated that our use of caricain as an enzyme capable of digesting peptides with two different types of toxicity has a sound scientific basis.

Glutagen Pty Ltd Maribyrnong Victoria Australia

RMIT University School of Applied Sciences Melbourne Australia

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