Definition: IPEX is a X-inked fatal disorder characterized by immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance (MIM.304930).
Patients typically present in infancy with severe diarrhea and failure to thrive. Most children die by 1 year of age without therapy. The diagnosis is established by genetic analysis, which often takes several weeks to complete and can sometimes delay crucial immunosuppressive treatment.
Synopsis
dysimmune enteropathy (autoimmune enteropathy)
- total or subtotal intestinal villous atrophy
- ileus and secretory diarrhea (intractable diarhhea)
- mucosal chronic inflammation
- failure to thrive
- eczema
severe recurrent infections
- abcesses
- fungal infections
variable autoimmune disorders
- autoimmune polyendocrinopathy
- autoimmunediabetes with absent islet cells (insulin-dependent diabetes mellitus or type I diabetes)
- hypothyroidism
- autoimmune hemolytic anemia
- autoimmune thrombocytopenia (idiopathic thrombopenic purpura)
- immune dysregulation
- possible T-cell activation
- autoantibodies
lymphadenopathy
death usually occurs in infancy or childhood
Histological synospsis
graft-vs-host disease-like changes (9/12 patients) (18820676)
coeliac disease-like pattern (2/12) (18820676)
enteropathy with a complete depletion of goblet cells (1/12) (18820676)
Circulating antibodies
anti-brush border pattern (11/12)
anti-goblet cell antibodies (1/12)
The histological presentation of autoimmune enteropathy is rather variable. However, a graft-vs-host disease-like pattern associated with positive anti-enterocyte antibodies is the most frequent intestinal presentation of IPEX syndrome, and constitutes a very valuable tool for pathologists to suspect this diagnosis. (18820676)
Etiology
mutation in the FOXP3 of the gene (11137992) at Xp11.23-q13.3
Immunochemistry
Patients with classic IPEX syndrome due to protein-truncating mutations in FOXP3 had markedly decreased staining of FOXP3+ T cells in the lamina propria and lymphoid aggregates. (17378693)
Patients with a missense mutation in FOXP3 had intact staining of FOXP3+ cells. (17378693)
Mouse model
scurfy mice (Foxp3 mutation)
See also
Immunodeficiencies
- primary immunodeficiencies
- X-linked immune syndromes
References
Patey-Mariaud de Serre N, Canioni D, Ganousse S, Rieux-Laucat F, Goulet O, Ruemmele F, Brousse N. Digestive histopathological presentation of IPEX syndrome. Mod Pathol. 2008 Sep 26. PMID: 18820676
Heltzer ML, Choi JK, Ochs HD, Sullivan KE, Torgerson TR, Ernst LM. A potential screening tool for IPEX syndrome. Pediatr Dev Pathol. 2007 Mar-Apr;10(2):98-105. PMID: 17378693
Bennett CL, Ochs HD. IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr. 2001 Dec;13(6):533-8. PMID: 11753102
Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001 Jan;27(1):20-1. PMID: 11137993
Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001 Jan;27(1):18-20. PMID: 11137992