Expanding the spectrum of IPEX: from new clinical findings to novel treatments

Abstract

Purpose of review: This review aims to provide an overview of recent research findings regarding immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, focusing on clinical and immunological novelties, as well as emerging treatment strategies, based on the published literature of the last few years.

Recent findings: While it is well known that IPEX can present with a wide range of atypical clinical manifestations, new and unique phenotypes continue to emerge, making it essential to maintain a high level of clinical suspicion both at the time of diagnosis and during follow-up. This unpredictability in clinical presentation is further compounded by the lack of a clear genotype-phenotype correlation. A valuable tool for monitoring comes from recent discoveries regarding the epigenetic signature of Tregs, which, by correlating with disease severity, could prove to be a useful biomarker for diagnosis and ongoing management. The use of biological agents is emerging as an alternative to traditional immunosuppression. Additionally, ongoing studies are exploring the feasibility of gene therapy through the introduction of the wild-type FOXP3 into peripheral CD4 + T cells.

Summary: Further research is needed to fully understand the variable clinical presentations of IPEX and optimize tailored therapies, ensuring better management and outcomes for affected individuals.

Box 1

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FIGURE 1

Atypical clinical manifestations of IPEX sorted by organ involvement. Captions in black correspond to known atypical manifestations, while those in red correspond to recently described atypical manifestations.