Epitope mapping of anti-amelogenin IgG in untreated celiac children.

Children with untreated celiac disease (CeD) may develop enamel defects, and children with severe CeD have significantly increased levels of IgG to amelogenin, which may interfere with normal amelogenesis depending on which epitope(s) they bind. Children with untreated CeD (n = 42), for whom CeD had been confirmed either by biopsy (n = 17, cohort 1) or by the presence of particularly high serum levels of anti-transglutaminase 2 (TG2) IgA (n = 25, cohort 2), were selected from 146 children with CeD, and 10 controls were selected from 34 children who did not have CeD. Samples from these 52 children were used for detailed IgG anti-amelogenin, X isoform (AMELX) epitope mapping using 31 overlapping, 10-22mer peptides in ELISA. Although sera from both groups showed reactivity to peptides containing sequences from the N and C terminus of AMELX, sera from children with CeD reacted more strongly to peptides from the central region (amino acids 75-150) containing both a binding site for transforming growth factor-β (TGF-β), as well as the enzymatic cleavage sites for matrix metalloproteinase-20 and for kallikrein-4. Antigen-specific extraction revealed that only IgG to the central region cross-reacted to gliadin. Thus, cross-reactive anti-gliadin/amelogenin IgG may affect normal amelogenesis by interfering with enzymatic degradation, proper folding, and/or TGF-β signaling in children with untreated CeD.