Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis1. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta2. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency3,4, and in patients diagnosed with coeliac disease5-7. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.
- MeSH
- ameloblasty metabolismus MeSH
- amelogenesis imperfecta * komplikace imunologie MeSH
- antigeny imunologie metabolismus MeSH
- autoimunitní polyglandulární syndromy * komplikace imunologie MeSH
- autoprotilátky * imunologie MeSH
- celiakie * komplikace imunologie MeSH
- imunoglobulin A imunologie MeSH
- lidé MeSH
- protein AIRE nedostatek MeSH
- proteiny imunologie metabolismus MeSH
- střeva imunologie metabolismus MeSH
- zubní sklovina imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AIRE protein, human MeSH Prohlížeč
- antigeny MeSH
- autoprotilátky * MeSH
- imunoglobulin A MeSH
- protein AIRE MeSH
- proteiny MeSH
