小柯机器人

以色列魏茨曼科学研究所Jakub Abramson和挪威卑尔根豪克兰大学医院Anette S. B. Wolff共同合作，近期取得重要工作进展。他们研究发现，APS-1和乳糜泻患者自身免疫性釉质发育不全。相关研究成果2023年11月22日在线发表于《自然》杂志上。

据介绍，成釉细胞是颌部特化的上皮细胞，在牙釉质的形成中起着不可或缺的作用。成釉作用依赖于多种成釉细胞来源的蛋白质，这些蛋白质作为羟基磷灰石晶体的支架。成釉细胞来源蛋白功能的丧失导致了一组罕见的先天性疾病，称为成釉不全症。由AIRE缺乏症引起的自身免疫性多腺体综合征1 型（APS-1）患者和确诊为乳糜泻的患者也存在釉质形成缺陷。然而，其根本机制仍不清楚。

研究人员发现绝大多数患有APS-1和乳糜泻的患者都会产生抗成釉细胞特异性蛋白的自身抗体（主要是IgA同种型），其表达是由AIRE在胸腺中诱导的。这反过来又导致中枢耐受性的崩溃，并随后产生干扰牙釉质形成的相应自身抗体。

然而，在乳糜泻疾病中，这种自身抗体的产生似乎是由外周对肠道抗原耐受性破坏驱动的，肠道抗原也在釉质组织中表达。这两种情况都是一种先前未确定的IgA依赖性自身免疫性疾病的例子，研究人员将其统称为自身免疫性釉质形成不全。

附：英文原文

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

Author: Gruper, Yael, Wolff, Anette S. B., Glanz, Liad, Spoutil, Frantisek, Marthinussen, Mihaela Cuida, Osickova, Adriana, Herzig, Yonatan, Goldfarb, Yael, Aranaz-Novaliches, Goretti, Dobe, Jan, Kadouri, Noam, Ben-Nun, Osher, Binyamin, Amit, Lavi, Bar, Givony, Tal, Khalaila, Razi, Gome, Tom, Wald, Tom, Mrazkova, Blanka, Sochen, Carmel, Besnard, Marine, Ben-Dor, Shifra, Feldmesser, Ester, Orlova, Elisaveta M., Hegeds, Csaba, Lamp, Istvn, Papp, Tams, 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

Issue&Volume: 2023-11-22

Abstract: 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.

DOI: 10.1038/s41586-023-06776-0

Source: https://www.nature.com/articles/s41586-023-06776-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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