Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease.

Autor: Gruper, Yael, Wolff, Anette S. B., Glanz, Liad, Spoutil, Frantisek, Marthinussen, Mihaela Cuida, Osickova, Adriana, Herzig, Yonatan, Goldfarb, Yael, Aranaz-Novaliches, Goretti, Dobeš, Jan, Kadouri, Noam, Ben-Nun, Osher, Binyamin, Amit, Lavi, Bar, Givony, Tal, Khalaila, Razi, Gome, Tom, Wald, Tomáš, Mrazkova, Blanka, Sochen, Carmel
Zdroj: Nature; Dec2023, Vol. 624 Issue 7992, p653-662, 10p
Abstrakt: 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.A large fraction of patients with APS-1 and coeliac disease develop enamel dystrophy, characterized by the presence of autoantibodies against the enamel matrix, which are generated through the breakdown of either central (APS-1) or peripheral (coeliac) tolerance to a battery of ameloblast-sepecific proteins. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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