Clinical and molecular aspects of autoimmune enteropathy and immune dysregulation, polyendocrinopathy autoimmune enteropathy X-linked syndrome

Purpose of review Autoimmune enteropathy (AIE) is a distinct cause of severe and persistent inflammatory diarrhea in children. Recent research data allowed us to gain a first insight in the pathogenesis of AlE. On the basis of this data, we will discuss new aspects of AlE emphasizing new diagnostic and therapeutic possibilities. Recent findings With the discovery of disease-causing mutations in the FOXP3 gene in patients with AlE, a dramatic advance in the understanding of AIE was made. Subsequent studies indicated that FOXP3 is a key transcription factor indispensable for regulatory functions of T cells pointing to a critical role of regulatory T-cell homeostasis in the development of AlE. Abnormal FOXP3 expression results in defective regulatory functions of T cells, which in turn cause a systemic T-cell-mediated autoaggressive disorder, now called immune dysregulation, polyendocrinopathy autoimmune enteropathy X-linked syndrome. Upon systematic review, we describe different phenotypes of immune dysregulation polyendocrinopathy autoimmune enteropathy X-linked syndrome, as well as immune dysregulation polyendocrinopathy autoimmune enteropathy X-linked-like forms of AlE, which are FOXP3 independent. No genotypephenotype correlation could be established so far. Summary On the basis of the profound immune dysregulation in AlE, new, most often T-cell-oriented treatment strategies were developed. The recent molecular advances in the understanding of AlE give a clear rational for the use of immunosuppression (combining steroids and tacrolimus or rapamycine) to stabilize AlE patients or to perform bone marrow transplantation in those who do not respond to immunomodulation.