| First Author | Gruper Y | Year | 2023 |
| Journal | Nature | Volume | 624 |
| Issue | 7992 | Pages | 653-662 |
| PubMed ID | 37993717 | Mgi Jnum | J:349397 |
| Mgi Id | MGI:7647106 | Doi | 10.1038/s41586-023-06776-0 |
| Citation | Gruper Y, et al. (2023) Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease. Nature 624(7992):653-662 |
| abstractText | Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis(1). 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(2). Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency(3,4), and in patients diagnosed with coeliac disease(5-7). 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. |
