Autoimmune enteropathy. Clinical and molecular aspects
PhD ceremony: Ms. N.D. Moes, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Autoimmune enteropathy. Clinical and molecular aspects
Promotor(s): prof. E.H.H.M. Rings, prof. F.M. Ruemmele
Faculty: Medical Sciences
Autoimmune enteropathy (AIE) is a rare cause of immunologically mediated chronic diarrhea in childhood. Characteristic of the disorder are circulating autoantibodies and destruction of the intestinal wall. Besides affecting the bowel, the disease comprises other manifestations of autoimmunity, such as diabetes mellitus, autoimmune thyreoïdia and autoimmune anemia or thrombocytopenia. AIE is a severe disease, often leading to mortality at a young age. More clarity about the pathophysiology of AIE is important for a better diagnosis and defining targeted therapeutic options. Also, more knowledge of the pathophysiology of AIE and intestinal regulatory T-cell (Treg)-function provides important information on normal immune function of the intestine.
This thesis focuses on the understanding of the disease by investigating its molecular background. The studies show that Treg-dysfunction is very important in the pathophysiology of AIE, but the results also suggest that it is not the only disease causing mechanism. In some patients a mutation in the FOXP3-gene is present, in others the cause is unclear. Our findings support the hypothesis that environmental factors can affect Treg-function. This has important implications for the ways in which these cells work and creates new opportunities for therapeutic interventions. We describe a large variety in the clinical presentation of AIE, which implies that the disease should be considered in a much larger number of patients. Finally, we examined the current immunosuppressive treatment in this disease, presenting molecular evidence for the efficacy of sirolimus.
Last modified: | 13 March 2020 01.08 a.m. |
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