title: Synthetic peptides reproducing tissue transglutaminase-gliadin complex neo-epitopes as probes for antibody detection in celiac disease patients' sera.
abstract: Celiac disease (CD) patients usually present high levels of circulating IgA antibodies directed to different antigens, in particular tissue transglutaminase (tTG), gliadin (Glia), and endomysium. A series of synthetic peptide constructs containing cross-linked tTG and Glia deamidated peptides have been synthesized. Peptides were tested in enzyme-linked immunosorbent assays against celiac disease patients' sera versus normal blood donors, and their conformational features were evaluated by molecular modeling techniques. Four peptides were recognized as epitopes by autoantibodies (IgG class) circulating in CD patients' sera before gluten-free diet. The peptide II, containing Ac-tTG(553-564)-NH2 sequence cross-linked with deamidated Ac-α2-Glia(63-71)-NH2, was able to identify specific disease antibodies with a sensitivity of 50% and a specificity of 94.4%. Structural conformations of the linear fragments Ac-tTG(553-564)-NH2 and Ac-α2-Glia(63-71)-NH2 and the corresponding cross-linked peptide II were calculated by molecular modeling. Results showed that cross-linking is determinant to assume conformations, which are not accessible to the linear fragments.
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, University of Florence , I-50019 Sesto Fiorentino, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Di Pisa
authors.forename: Simona
authors.initials: S
authors.lastname: Pascarella
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sabatino
authors.forename: Feliciana
authors.initials: F
authors.lastname: Real-Fernández
authors.forename: Mario
authors.initials: M
authors.lastname: Chelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Renzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Calabrò
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D002446:Celiac Disease / Q000097:blood* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D005903:Gliadin / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D000939:Epitopes; D010455:Peptides; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins