According to a recent study, damage to tooth enamel common in celiac disease may be caused by an autoimmune reaction triggered by intestinal or dietary proteins. The Institute of Dentistry at the University of Eastern Finland participated in the international collaborative study, the results of which were published in Nature .
Autoimmune amelogenesis imperfecta in patients with APS-1 and celiac disease Summary Ameloblasts are specialized epithelial cells that play an indispensable role in the formation of tooth enamel: amelogenesis. Amelogenesis depends on multiple proteins derived from ameloblasts that function as a scaffold for hydroxyapatite crystals. 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) and in patients diagnosed with celiac disease . However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and celiac disease develop autoantibodies (mainly 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 the subsequent generation of the corresponding autoantibodies that interfere with enamel formation . However, in celiac disease, the generation of such autoantibodies appears to be driven by impaired 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 call autoimmune amelogenesis imperfecta . |
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Researchers found a link between disorders of tooth enamel development seen in certain autoimmune diseases, such as celiac disease, and the appearance of autoantibodies against proteins responsible for the formation of healthy tooth enamel.
Celiac disease is one of the most common autoimmune diseases today, developing mainly in childhood and affecting 1 in 100 people.
The small intestine protein transglutaminase 2 (TGM2) enzyme plays a key role in triggering celiac disease by modifying the protein gliadin , a component of dietary gluten , in the intestine. The immune system of affected people reacts to the enzyme/gliadin complex and produces autoantibodies against both proteins. The appearance of antibodies against TGM2 is so disease-specific that it is also used to detect celiac disease.
Although the main symptom of celiac disease is inflammation of the intestine, it is well known that in children affected by the disease, tooth enamel often does not develop correctly. Often, the child’s dentist is the first to suspect celiac disease.
It was long thought that dental manifestations in celiac disease were caused primarily by malabsorption associated with intestinal inflammation. However, the present study demonstrated for the first time that defects in enamel formation can be caused by antibodies produced against proteins from the intestine or diet, by binding to proteins that control the development of tooth enamel. This is because tooth enamel proteins have binding sites for antibodies similar to, for example, the TGM2 enzyme and the kappa-casein protein in cow’s milk.
The study involved researchers from the Czech Republic, Israel, Norway, Hungary and Finland who followed 48 adults and 21 children with celiac disease, as well as 28 APS1 patients with another autoimmune disease, APS1.
The immune response related to enamel damage was also studied in animal models. University Professor Szabolcs Felszeghy from the University of Eastern Finland contributed to the study by demonstrating, among other things, that antibodies against TGM2 in celiac patients can bind to proteins in tooth enamel and therefore interfere with tooth development.
