|Other names||Autoimmune enteropathy type 1|
|IPEX syndrome is inherited via X-linked recessive|
|Causes||FOXP3 gene mutation|
|Diagnostic method||Family history, Genetic test|
|Treatment||TPN(nutritional purpose), Cyclosporin A and FK506, Bone marrow transplant|
Immunodysregulation polyendocrinopathy enteropathy X-linked (or IPEX) syndrome is a rare disease linked to the dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the regulatory T cell lineage. It leads to the dysfunction of regulatory T-cells and the subsequent autoimmunity. The disorder is one of the autoimmune polyendocrine syndromes and manifests with autoimmune enteropathy, psoriasiform or eczematous dermatitis, nail dystrophy, autoimmune endocrinopathies, and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid. Management for IPEX has seen limited success in treating the syndrome by bone marrow transplantation.
Symptoms and signs
Some of the symptoms and signs of IPEX syndrome are the following:
Mutation of FOXP3 leading to expression of malfunctioning protein is often localised in DNA-binding domain called the forkhead domaine. The truncated protein can not bind to its binding-spot on the DNA and thus its function concerning T regulatory lymphocytes development and functioning is impaired. The absence or dysfunction of regulatory T cells is the cause of autoimmune symptoms.
Data from 2018 describes over 70 mutations in FOXP3 gene leading to IPEX syndrome. Nonetheless, this number is still changing with new cases and discoveries coming. For example in 2010 there were only 20 mutations of FOXP3 known in the literature.
This autoimmunity called IPEX is an attack from the body's own immune system against the body's own tissues and organs. Early age onset of this disease in males causes severe enlargement of the secondary lymphoid organs, and insulin dependent diabetes[medical citation needed]
This condition indicates the loss of CD4+CD25+ T regulatory cells, and express the transcription factor Foxp3. Foxp3 decrease is a consequence of unchecked T cell activation, which is secondary to loss of regulatory T cells.
The diagnosis of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is consistent with the following criteria:
- TPN (nutritional purpose)
- Cyclosporin A and FK506
- Sirolimus (should FK506 prove non-effective)
- Granulocyte colony stimulating factor
- Bone marrow transplant
There is as well a special mouse model simulating the development and progression of the IPEX syndrome. The model mice are called "scurfy mice" and they have had 2 base pairs inserted within the Foxp3 gene. Consequently, this leads to a frameshift and the expressed protein is truncated, causing the same effects as FOXP3 mutation in humans. The mice suffer from enlarged spleen and lymph nodes, redness in eyes and skin abnormalities. The mice as well suffer from immunity problems and after approximately 3 weeks they die.
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