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

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

“…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].…”

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

“…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).…”

“…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).…”

“…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).…”

Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

“…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.…”