IPEX Syndrome: Clinical Profile, Biological Features, and Current Treatment

Abstract

Children carrying mutations in the forkhead box p3 (FOXP3) gene are affected by the syndrome known as Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX). Early onset severe enteropathy, Type-1 diabetes (T1D) and eczema with elevated IgE serum levels are the hallmarks of the disease. Mortality is generally high within the first year of life, although some patients can partially respond to conventional immunosuppression showing clinical improvement. Progress in understanding the pathogenesis of IPEX have been made possible by the recognition that FOXP3 is the driving force for the function of naturally occurring regulatory T cells, a T-cell subset specialized in controlling immune responses. However, many open questions concerning the disease mechanisms, the indications for genetic screening and appropriate treatment of IPEX syndrome remain unanswered. In addition, several patients presenting IPEX-like symptoms do not carry mutations in the FOXP3 gene. In the present chapter, we will (1) summarize the latest findings on the biologic function of FOXP3 and its role in immune regulation, (2) highlight the most relevant signs for a correct diagnosis of IPEX syndrome, and (3) provide indications for the development of more targeted therapeutic strategies for the treatment of this devastating pediatric autoimmune disease.