Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.