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PMID: 23060872 Published · epublish English Journal Article

Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity.

Frontiers in immunology ·Vol. 3 ·2012-00-00 ·Pages 211

Barzaghi F, Passerini L, Bacchetta R

Abstract

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency (PID) due to mutations of FOXP3, a key transcription factor for naturally occurring (n) regulatory T (Treg) cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type-1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia can develop in patients who survive the initial acute phase. The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is hematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease. This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

Keywords
FOXP3 HSCT IPEX Treg autoimmune enteropathy neonatal diabetes neonatal eczema
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Barzaghi Federica
Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute Milan, Italy ; Vita Salute San Raffaele University Milan, Italy.
Passerini Laura
Bacchetta Rosa
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Article Info
Journal
Frontiers in immunology
Abbr.
Front Immunol
ISSN
1664-3224
DOI
10.3389/fimmu.2012.00211
Published
2012-00-00
Epub
2012-00-31
Pages
211
Language
English
Region
Switzerland
NLM ID
101560960
PMCID
PMC3459184
Grants
Telethon · TGT11A04 · Italy
External Links
PubMed source DOI: 10.3389/fimmu.2012.00211 PMC Full Text View journal details
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