RESUMEN
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.
Asunto(s)
Amelogénesis Imperfecta , Autoanticuerpos , Enfermedad Celíaca , Poliendocrinopatías Autoinmunes , Humanos , Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/inmunología , Autoanticuerpos/inmunología , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/inmunología , Inmunoglobulina A/inmunología , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/inmunología , Proteínas/inmunología , Proteínas/metabolismo , Ameloblastos/metabolismo , Esmalte Dental/inmunología , Esmalte Dental/metabolismo , Proteína AIRE/deficiencia , Antígenos/inmunología , Antígenos/metabolismo , Intestinos/inmunología , Intestinos/metabolismoRESUMEN
Food allergy is a potentially life-threatening condition affecting almost 10% of children, with an increasing incidence in the last few decades. It is defined as an immune reaction to food, and its pathogenesis may be IgE mediated, mixed IgE and non-IgE mediated, or non-IgE mediated. Potentially all foods can cause food allergy, but a minority of foods are responsible for the vast majority of reactions reported. A good clinical history is crucial for an accurate diagnosis. Allergy tests, including the skin prick test and measurement of specific IgE antibodies, are useful tools in the case of IgE-mediated or mixed allergy but have not been shown to be of any help in delayed allergic reactions to foods.
