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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; Besnard, Marine; Ben-Dor, Shifra; Feldmesser, Ester; Orlova, Elisaveta M; Hegedűs, Csaba; Lampé, István; Papp, Tamás; Felszeghy, Szabolcs; Sedlacek, Radislav; Davidovich, Esti; Tal, Noa; Shouval, Dror S; Shamir, Raanan; Guillonneau, Carole; Szondy, Zsuzsa; Lundin, Knut E A; Osicka, Radim; Prochazka, Jan; Husebye, Eystein S; Abramson, Jakub
Nature (London), 12/2023, Letnik: 624, Številka: 7992Journal Article
Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis . 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 imperfecta . Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency , and in patients diagnosed with coeliac disease . 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.
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in: SICRIS
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