Enamel defects associated with coeliac disease: putative role of antibodies against gliadin in pathogenesis

Abstract

Enamel defects in the permanent teeth of patients with coeliac disease (CD) are often reported as an atypical manifestation, sometimes being suggestive of an undiagnosed atypical disease. We proposed to explore the pathogenesis of these oral defects, which are poorly studied. Sequence analyses of proteins from gluten (gliadins) and of proline-rich enamel proteins (amelogenin and ameloblastin) suggested the presence of common antigenic motifs. Therefore, we analyzed, by ELISA and western blotting, the reactivity of sera from patients with CD against gliadin and enamel-derived peptides. Correlation analyses between the levels of specific antibodies against gliadin and enamel derived peptides and inhibition experiments confirmed the presence of cross-reactive antibodies. Immunoblot analysis revealed that the most prominent component in enamel matrix derivative (of approximately 18.6 kDa), identified by an amelogenin-specific antibody, is recognized by sera from patients with CD; in addition, several fractions of pure gliadin were recognized by amelogenin-specific antibody. In agreement, sera from mice immunized with enamel matrix-derived proteins generated antibodies that recognized a peptide (of approximately 21.2 kDa) derived from gliadin. In conclusion, antibodies against gliadin generated in patients with CD can react in vitro with a major enamel protein. The involvement of anti-gliadin serum in the pathogenesis of enamel defects in children with untreated CD can be hypothesized on the basis of these novel results.

The Osteological Paradox 20 Years Later: Past Perspectives, Future Directions

“…Research among living people indicates that children with enamel hypoplasia are of significantly shorter stature than those without them (Lukacs et al 2001). Other risk factors for enamel defects include low prenatal vitamin D (Schroth et al 2014), infections or high fever during childhood (Ford et al 2009;Ghanim et al 2013;Souza et al 2012), celiac disease (Munoz et al 2012), and immunodeficiency diseases (Meighani et al 2011). The established associations between enamel hypoplasia and poor health and the fact that enamel does not remodel after formation makes these lesions particularly useful for paleopathological analyses, some of which have begun to explore the developmental origins of poor adult health (see above).…”

Histopathological findings in the oral mucosa of celiac patients

“…Atypical forms include extra-intestinal manifestations as iron-deficiency anemia, dermatitis herpetiformis, osteoporosis and osteopenia, recurrent aphtous stomatitis (RAS) and dental enamel defects (DED); silent forms are characterized by absence of symptoms with progressive flattening of intestinal villi and positivity to serological tests while potential forms by absence of symptoms and of histological alterations but positivity to serological tests (3)(4)(5). The only treatment of CD is a lifelong adherence to a gluten-free diet (GFD), which usually results in remission (1,2).…”

“…Celiac disease (CD) is a lifelong immune-mediated disorder triggered by the ingestion of gluten, a protein contained in wheat, rye and barley, in genetically susceptible people (1,2).…”

Celiac Disease and Its Impact on the Oral Health Status – Review of the Literature

“…The cause of that is probably the similarity of amino acids composition of gliadin and that of enamel proteins with a particularly high content of proline which, in turn, together with glutamine, is to be responsible for immunological properties of gliadin in genetically predisposed people [30].…”