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Epitope mapping of anti-amelogenin IgG in untreated celiac children
Sanja Petronijevic1, Solveig Stig1, Trond S Halstensen1,2
1Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Insights
Children with untreated celiac disease (CeD) show increased IgG antibodies to amelogenin, potentially causing enamel defects. These antibodies may interfere with tooth enamel formation by targeting specific protein regions.
Area of Science:
- Immunology
- Pediatric Dentistry
- Gastroenterology
Background:
- Untreated celiac disease (CeD) is linked to dental enamel defects in children.
- Elevated IgG antibodies to amelogenin are observed in children with severe CeD.
- Amelogenin is crucial for tooth enamel formation, and antibodies may disrupt this process.
Purpose of the Study:
- To investigate IgG antibody epitope mapping to amelogenin (AMELX) in children with untreated CeD.
- To determine if anti-amelogenin antibodies cross-react with gliadin, a gluten protein.
- To explore the potential mechanisms by which these antibodies affect amelogenesis.
Main Methods:
- Selected 42 children with untreated CeD and 10 healthy controls.
- Performed IgG anti-AMELX epitope mapping using 31 overlapping peptides via ELISA.
- Utilized antigen-specific extraction to identify cross-reactivity with gliadin.
Main Results:
- Sera from CeD patients showed stronger reactivity to central AMELX peptides (amino acids 75-150) compared to controls.
- This central region contains binding sites for TGF-β and cleavage sites for MMP-20 and KLK4.
- Antigen-specific extraction revealed that IgG targeting the central AMELX region cross-reacted with gliadin.
Conclusions:
- Cross-reactive IgG antibodies to gliadin and amelogenin are present in children with untreated CeD.
- These antibodies may impair amelogenesis by interfering with protein folding, enzymatic degradation, or TGF-β signaling.
- This finding provides a potential explanation for enamel defects observed in CeD patients.
Abstract:
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.
