Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: Inconsistent correlation between forkhead box protein 3 expression and disease severity

Gambineri, Eleonora; Perroni, L; Passerini, Laura; Bianchi, Lucia; Doglioni, Claudio; Meschi, Franco; Bonfanti, Riccardo; Sznajer, Yves; Tommasini, Alberto; Lawitschka, Anita; Junker, Anne; Dunstheimer, Desirée; Heidemann, Peter P.H.; Cazzola, G; Cipolli, Marco; Friedrich, Wilhelm; Janić, Dragana; Azzi, Nadira; Richmond, Erick; Vignola, Silvia; Barabino, A.; Chiumello, G; Azzari, Chiara; Roncarolo, Maria Grazia; Bacchetta, Rosa

doi:10.1016/j.jaci.2008.09.027

Cited by 199 publications

(209 citation statements)

References 38 publications

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“…Usually, IPEX patients show a broad range of autoantibodies because of adaptive immune dysregulation. With over 60 FOXP3 mutations reported up to now, observations from the clinical phenotype reported for these mutations have led to postulations of genotype/phenotype relationships [100].…”

Section: Immune Dysregulation Polyendocrinopathy Enteropathy X-linmentioning

confidence: 99%

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Torres¹,

López-Casado²,

León³

et al. 2017

Physiology and Pathology of Immunology

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The immune system is responsible for the defense of the organism. It controls what is introduced into it and identifies it as self from non-self. The defensive mechanisms activated by the immune system are directed against pathological microbes and toxic or allergenic proteins, and it must avoid responses that produce excessive damage of self-tissues, inducing tolerance to avoid autoimmunity and other immunopathologies. Regulatory Tcells play an essential role in these active processes, using several distinct suppressive mechanisms. The immune dysregulatory diseases result from defects affecting regulatory T cell development and/or function, including the impact of essential genes mutations for Tregulatory cell functions and the associated autoimmune syndromes.

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Section: Immune Dysregulation Polyendocrinopathy Enteropathy X-linmentioning

confidence: 99%

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Torres¹,

López-Casado²,

León³

et al. 2017

Physiology and Pathology of Immunology

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“…The most prominent genetic susceptibility factors for autoimmune thyroid disease (AITD) in particular are located in the HLA region and conferred by a specific CTLA4 single nucleotide polymorphism (SNP) (1,2,3). One of the rare X-linked syndromes that specifically predispose affected boys to the development of severe multiorgan autoimmune diseases with unclear genotype-phenotype correlation is the 'immune dysregulation polyendocrinopathy enteropathy X-linked' (IPEX) syndrome (4). It is caused by frameshift and missense mutations in the fork-head DNA-binding box protein P3 (FOXP3) gene on Xp11.23 that impairs the function of the encoded protein (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…One of the rare X-linked syndromes that specifically predispose affected boys to the development of severe multiorgan autoimmune diseases with unclear genotype-phenotype correlation is the 'immune dysregulation polyendocrinopathy enteropathy X-linked' (IPEX) syndrome (4). It is caused by frameshift and missense mutations in the fork-head DNA-binding box protein P3 (FOXP3) gene on Xp11.23 that impairs the function of the encoded protein (4,5). FOXP3 is primarily but not exclusively expressed in CD4 C CD25 C regulatory T (Treg) cells that are essential for maintaining the balance between immune tolerance and suppression (5,6,7).…”

Section: Introductionmentioning

confidence: 99%

“…FOXP3 is primarily but not exclusively expressed in CD4 C CD25 C regulatory T (Treg) cells that are essential for maintaining the balance between immune tolerance and suppression (5,6,7). Partial FOXP3 deficiency is associated with overstimulation of T cells, which in turn is an essential component of many immune disorders and autoimmune phenomena, whereas a complete lack of the protein is the root for severe forms of the IPEX syndrome (4,5,6,8). Although the majority of affected males die within the first 2 years of life, some of them may survive into adulthood (4,9).…”

Section: Introductionmentioning

confidence: 99%

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Concurrent FOXP3- and CTLA4-associated genetic predisposition and skewed X chromosome inactivation in an autoimmune disease-prone family

Seidel

Rami

Item

et al. 2012

European Journal of Endocrinology

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CLTA4 is relevant for FOXP3C Treg cells, and the link between skewed X chromosome inactivation (XCI) and autoimmunity is recognized. The observation of immune dysregulation polyendocrinopathy enteropathy X-linked syndrome and multiorgan endocrine autoimmune phenomena in various members of one family, associated with a CTLA4 polymorphism and skewed XCI, provides an in vivo model of how mechanisms of immune dysregulation may cooperate.

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“…Without treatment, many patients die in the first 2 years of life because of sepsis or FTT. 2 Management of children with autoimmune enteropathy is challenging. Supportive care includes total parental nutrition (TPN), blood transfusions, treatment of autoimmune manifestations together with longterm immunosuppressive drug treatment, which may reduce clinical manifestations, but is not curative and drug toxicities limit this approach.…”

mentioning

confidence: 99%