Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders: an evolving web of heritable autoimmune diseases

Curr Opin Pediatr. 2013 Dec;25(6):708-14. doi: 10.1097/MOP.0000000000000029.


Purpose of review: To summarize recent progress in our understanding of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders.

Recent findings: A number of Mendelian disorders of immune dysregulation and autoimmunity have been noted to result from defects in T regulatory cell, development and function. The best characterized of these is IPEX, resulting from mutations affecting FOXP3. A number of other gene defects that affect T regulatory cell function also give rise to IPEX-related phenotypes, including loss-of-function mutations in CD25, STAT5b and ITCH. Recent progress includes the identification of gain-of-function mutations in STAT1 as a cause of an IPEX-like disease, emerging FOXP3 genotype/phenotype relationships in IPEX, and the elucidation of a role for the microbiota in the immune dysregulation associated with regulatory T cell deficiency.

Summary: An expanding spectrum of genetic defects that compromise T regulatory cell function underlies human disorders of immune dysregulation and autoimmunity. Collectively, these disorders offer novel insights into pathways of peripheral tolerance and their disruption in autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autoantibodies / immunology
  • Autoimmunity / genetics
  • Autoimmunity / immunology
  • Diabetes Mellitus, Type 1 / congenital
  • Diarrhea / genetics
  • Diarrhea / immunology*
  • Diarrhea / pathology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / immunology*
  • Genetic Diseases, X-Linked / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Immune System Diseases / congenital
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / pathology
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Intestinal Diseases / genetics
  • Intestinal Diseases / immunology*
  • Intestinal Diseases / pathology
  • Male
  • Mutation / genetics
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*
  • Polyendocrinopathies, Autoimmune / pathology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / immunology*


  • Autoantibodies
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Repressor Proteins
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • ITCH protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

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