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