IN-VITRO ACTIVITIES OF A-GLIADIN-RELATED SYNTHETIC PEPTIDES - DAMAGING EFFECT ON THE ATROPHIC CELIAC MUCOSA AND ACTIVATION OF MUCOSAL IMMUNE-RESPONSE IN THE TREATED CELIAC MUCOSA

Background: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have nor been fully elucidated. Previous in v itro studies have suggested the presence of active sequences in the NH 2-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has b een investigated. Methods: Organ culture of jejunal mucosa from untrea ted and treated coeliac patients was used. In the first system enteroc yte height was used as a measure of peptide toxicity; in the second sy stem evidence of activated mucosal cell-mediated immune response was s ought. Results: Peptides 31-55 and 31-43 were active on untreated coel iac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molec ules and the appearance of CD25-positive cells. Conclusions: Our resul ts suggest that 31-43 and 44-55 A-gliadin peptides are both active, ev en if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.