Effects of Gliadin-Derived Peptides from Bread and Durum Wheats on Small Intestine Cultures from Rat Fetus and Coeliac Children

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Abstract
Summary: Peptic-tryptic-cotazym (PTC) digests were obtained, simulating in vivo protein digestion, from albumin, globulin, gliadin and glutenin preparations from hexapiod (bread) wheat as well as from diploid (monococcum) and tetraploid (durum) wheat gliadins. The digest from bread wheat gliadins reversibly inhibited in vitro development and morphogenesis of small intestine from 17-day-old rat fetuses, whereas all the other digests (obtained both from nongliadin fractions and from gliadins from other wheat species) were inactive. The PTC-digest from bread wheat gliadins was also able to prevent recovery of and to damage the in vitro cultured small intestinal mucosa from patients with active coeliac disease (gluteninduced entheropathy). The PTC-digest from durum wheat gliadins caused a much less adverse effect on this human pathologic tissue culture system. Speculation: When tested with different in vitro systems, bread wheat gliadin peptides active in coeliac disease displayed several peculiar biologic activities including an immunogenic character in susceptible individuals (Z), a probable immunomediated cytotoxic activity on small intestinal mucosa specimens from coeliac patients (6-10, 13-15, 17), and a probable direct cytotoxic activity on developing rat fetal intestine (5). In fact, these peptides induce the following: (I) proliferation of peripheral blood lymphocytes from coeliac patients as well as from many first degree relatives of coeliacs and from only a few normal controls; (2) damage of the in vitro cultured small intestinal mucosa of patients with active coeliac disease; and (3) reversible inhibition of the in vitro development of fetal rat intestine. Although no one of the mentioned in vitro systems can be considered a model fully representative of coeliac disease, it is likely that each one of them highlights a different important feature underlying the appearance of the small intestine lesion in coeliac patients ingesting bread wheat gliadin peptides. Peptide mixtures obtained by enzymic digestion of the gliadin fraction from hexaploid (bread) wheats significantly differ from those from tetraploid (durum) wheat gliadins for their higher toxicity toward cultures of intestine from rat fetuses or coeliac children. However, gliadin peptides from both bread and durum wheats are capable of inducing proliferation of peripheral blood lymphocytes from coeliac patients thus suggesting a similar immunogenic character (2). We suggest that durum wheat gliadins peptides are in vitro less toxic than bread wheat gliadins peptides for the small intestinal mucosa of coeliacs as they have less direct cytotoxic effect on the enterocyte; moreover, durum wheat products (e.g., spaghetti), as compared to bread wheat products (e.g., bread and biscuits), migh present a lower risk for patients suffering for coeliac disease or other wheat intolerances.

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