IPEX syndrome from diagnosis to cure, learning along the way

J Allergy Clin Immunol. 2024 Mar;153(3):595-605. doi: 10.1016/j.jaci.2023.11.021. Epub 2023 Nov 30.

Abstract

In the past 2 decades, a significant number of studies have been published describing the molecular and clinical aspects of immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome. These studies have refined our knowledge of this rare yet prototypic genetic autoimmune disease, advancing the diagnosis, broadening the clinical spectrum, and improving our understanding of the underlying immunologic mechanisms. Despite these advances, Forkhead box P3 mutations have devastating consequences, and treating patients with IPEX syndrome remains a challenge, even with safer strategies for hematopoietic stem cell transplantation and gene therapy becoming a promising reality. The aim of this review was to highlight novel features of the disease to further advance awareness and improve the diagnosis and treatment of patients with IPEX syndrome.

Keywords: FOXP3; Regulatory T cells; TSDR; gene therapy; genetic autoimmunity; immune dysregulation.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / congenital*
  • Diarrhea
  • Forkhead Transcription Factors / genetics
  • Genetic Diseases, X-Linked* / diagnosis
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / therapy
  • Humans
  • Immune System Diseases* / congenital*
  • Immune System Diseases* / diagnosis
  • Immune System Diseases* / genetics
  • Immune System Diseases* / therapy
  • Intestinal Diseases* / diagnosis
  • Intestinal Diseases* / genetics
  • Mutation
  • Polyendocrinopathies, Autoimmune* / diagnosis
  • Polyendocrinopathies, Autoimmune* / genetics
  • Polyendocrinopathies, Autoimmune* / therapy
  • T-Lymphocytes, Regulatory

Substances

  • Forkhead Transcription Factors

Supplementary concepts

  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome