Ipex Syndrome -Clinical Findings
The most prominent IPEX symptoms include early onset diarrhea secondary to autoimmune enteropathy, multiple endocrinopathies including insulin-dependent type 1 diabetes mellitus, thyroiditis, and, rarely, adrenal insufficiency. Autoimmune hemolytic anemia, thrombocytopenia, and neutropenia are common complications. Eczema is the most frequent pathology of the skin, but erythematous and psoriasiform dermatitis and alopecia universalis have been reported. Lymphadenopathy and hepatosplenomegaly are less common.132 There is loss of small bowel villi, and lymphocytic infiltrates in the intestinal mucosa, the pancreas, thyroid, lung, and liver. Immunologic abnormalities include elevated serum IgA and IgE concentrations and the absence of CD4+CD25+ FOXP3+ regulatory T cells.
IPEX is caused by mutations in the FOXP3 gene located in the centromeric region of the X chromosome.133 The transcription factor FOXP3 acts as a transcriptional repressor of the IL-2, IL-4, and Interferon (IFN)- promoters by interfering with the cytokine regulator, NFAT (nuclear factor of activated T cells).134
Treatment – hematopoietic stem cells from a matched sibling
Immunosuppressive drugs such as cyclosporine A, tacrolimus, sirolimus, and glucocorticoids provide temporary remission. Allogeneic hematopoietic stem cell transplantation can cure this disease.135
An IPEX-like phenotype has been associated with mutations in CD25, resulting in a complete lack of the IL-2 receptor chain (CD25). In addition to the characteristic autoimmune manifestations of IPEX, both patients with CD25 deficiency suffered from opportunistic infections, as expected from defective IL-2R signaling.136,137 Because of these SCID-like features, one patient was successfully transplanted with hematopoietic stem cells from a matched sibling.136