IN-VITRO MUCOSAL DIGESTION OF SYNTHETIC GLIADIN-DERIVED PEPTIDES IN CELIAC-DISEASE

Two celiac-active synthetic peptides derived from the A-gliadin struct ure corresponding to residues 8-19 (LQPQNPSQQQPQ) and to 11-19 were di gested in vitro with small intestinal mucosa from children with celiac disease in remission and from normal children. The products of digest ion were separated into two fractions on the basis of M(r)<400 and M(r )>400 by gel permeation chromatography and subjected to amino acid ana lysis. After digestion of the dodecapeptide with celiac mucosa, 71+/-1 4% (molar) of the total digestion products remained in the M(r)>400 fr action. Glutamine, proline, serine, and asparagine were the major amin o acids present. Glutamine, proline, and leucine were the major amino acids in the M(r)<400 fraction. The M(r)>400 fraction from the celiac mucosal digestion of the nonapeptide was of similar composition to the corresponding fraction from the dodecapeptide and represented 78+/-15 % of the total products. Digestion of the two peptides with normal muc osa gave lower amounts of products in the M(r)>400 fraction, but they were of similar composition to the corresponding fractions from the ce liac mucosal digestion. Peptides such as NPSQQQP and QNPSQQQ may be pr esent in the M(r)>400 fractions since glutamine and proline are presen t in the approximate ratio of 2:1, respectively. The results indicate a defect in the mucosal digestion of peptides which are active in an a nimal model of celiac disease.