Clinical and molecular aspects of autoimmune enteropathy and immune dysregulation, polyendocrinopathy autoimmune...

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 AIE. On the basis of this data, we will discuss new aspects of AIE emphasizing new diagnostic and therapeutic possibilities.

With the discovery of disease-causing mutations in the FOXP3 gene in patients with AIE, 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 AIE. 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 AIE, which are FOXP3 independent. No genotype-phenotype correlation could be established so far.

On the basis of the profound immune dysregulation in AIE, new, most often T-cell-oriented treatment strategies were developed. The recent molecular advances in the understanding of AIE give a clear rational for the use of immunosuppression (combining steroids and tacrolimus or rapamycine) to stabilize AIE patients or to perform bone marrow transplantation in those who do not respond to immunomodulation.