Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX) Workup
- Author: Satyen M Gada, MD; Chief Editor: Harumi Jyonouchi, MD more...
Molecular genetic testing for immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome can be performed by DNA sequencing of the FOXP3 gene and mutation analysis. Sixty percent of patients with IPEX syndrome have an identifiable mutation in FOXP3. Patients with IPEX-like conditions with no identifiable mutation in FOXP3 may have mutations in the regulatory sequences in the FOXP3 gene or in pathways related to regulatory T-cell development or function.[18, 19]
While genetic testing modalities remain the criterion standard, one paper does highlight autoantibody markers to harmonin and villin as a possible diagnostic tool for IPEX syndrome; however, more research is needed.
Although not diagnostic, other laboratory tests may support the diagnosis of IPEX syndrome.
Thyroid-stimulating hormone (TSH), FT4, and thyroid antibodies are used to evaluate for autoimmune thyroid disease.
Serum glucose test, oral glucose tolerance test, and anti-islet cell antibodies testing are used to assess insulin-dependent diabetes. Anti–glutamic acid decarboxylase (GAD) antibodies and anti-insulin antibodies have also been reported in patients with IPEX syndrome.
CBC count with differential is used to evaluate for autoimmune hemolytic anemia, thrombocytopenia, and/or neutropenia. Marked eosinophilia has been described. If anemia is present, evaluation for autoantibody production with Coombs testing may be performed. Patients with IPEX syndrome usually have intermittent eosinophilia.
BUN and creatinine level measurement and urinalysis with microscopy is used to assess evidence of autoimmune renal disease.
Liver function tests assess for evidence of autoimmune liver disease.
Serum immunoglobulin E (IgE) and immunoglobulin A (IgA) levels are usually elevated in patients with IPEX syndrome.
Flow cytometry of peripheral blood CD4+ CD25+ FOXP3+ usually reveals decreased T cells in patients with IPEX syndrome.
Imaging studies are not routinely required for the diagnosis and management of IPEX syndrome.
Consider targeting imaging studies to evaluate for sinus disease and potential bronchiectasis.
Quantitative immunoglobulins (immunoglobulin G [IgG], immunoglobulin M [IgM], immunoglobulin A [IgA]), antibody response to protein and polysaccharide antigens, and B-cell subsets are normal. Low immunoglobulin levels in a patient with IPEX syndrome is suggestive of a significant protein-losing enteropathy.
T-cell subsets, in vitro lymphocyte proliferative response to mitogens, and delayed-type hypersensitivity are normal. Increased TH-2 cytokine (interleukin [IL]-4, IL-5, IL-13) and decreased TH-1 cytokine (interferon [INF]-γ) expression has been reported in patients with IPEX syndrome.
Although autoimmune neutropenia is commonly found in IPEX syndrome, neutrophil function is preserved.
Patients with IPEX syndrome have normal serum complement levels.
Endoscopy (upper and lower) with biopsy is used to evaluate for enteropathy. Skin biopsy is used to characterize dermatitis.
All 3 of the histologic findings below are associated with various degrees of villous atrophy and cellular inflammatory infiltrate.
Graft versus host disease –like pattern associated with positive antienterocyte antibodies (most common) 
Celiac disease –like pattern 
Enteropathy with complete depletion of goblet cells was also associated with IPEX syndrome.
Lymphocytic infiltrate with destruction of exocrine tissue and loss of islet cells is observed.
Dermatologic findings include the following:
Lymphocytic dermal infiltrate
Thyroid findings include the following:
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