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Immunology Diagnostic Laboratory

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX)

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IPEX

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is an X-linked syndrome that presents with systemic autoimmunity that most commonly affects the bowel, pancreas, thyroid and skin. Patients frequently develop additional autoimmune symptoms as well. IPEX is caused by mutations in the FOXP3 gene, which leads to absence of functional regulatory T cells. The disease should be suspected particularly in males who have severe, early-onset chronic diarrhea combined with diabetes, thyroid disease and eczema.

Key Clinical Features

  • Enteropathy: Watery diarrhea, usually early onset (< 6 months old)
  • Endocrinopathy: Type I diabetes or thyroiditis most common
  • Dermatitis: Eczema most common but may be psoriasiform, pemphigoid, etc.
  • Other Autoimmunity: Autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), autoimmune neutropenia, autoimmune hepatitis, nephropathy, etc.
  • Elevated IgE

Molecular Defects Associated With IPEX

  • FOXP3 (forkhead box P3)
    • Inheritance: X-linked
     

Molecular Defects Associated With IPEX-Like Disease

  • CD25 (IL-2 receptor α-chain)
    • Inheritance: Autosomal recessive
    • In addition to IPEX-like symptoms, CD25 deficiency is associated with susceptibility to viral infections (CMV pneumonitis) and poor T-cell proliferation to mitogenic stimuli. IgE normal or mildly elevated.
     
  • STAT5B (signal transducer and activator of transcription 5B)
    • Inheritance: Autosomal recessive
    • In addition to IPEX-like symptoms, STAT5B deficiency is associated with decreased T cell and NK cells numbers, increased susceptibility to viral infections (varicella, herpes, etc.), and marked growth delay with normal serum growth hormone levels but low insulin-like growth factor-1 (IGF-1).
     

Suggested Testing Approach

CIIT Ipex Training Approach

Specimen Requirements

  • Flow Cytometry Only or Flow Cytometry + Gene Sequencing: 5-7 cc whole blood in heparin sodium anticoagulant (green top tube) shipped overnight at ambient temperature. Please include 5-7 cc of whole blood from a normal individual in a separate tube as a control for flow cytometry studies in any shipped samples.
  • Gene Sequencing Only: 2-5 cc whole blood in heparin sodium or EDTA anticoagulant. Ship overnight at ambient temperature.
  • Alternative sources of DNA can be used as well (buccal swabs, CVS, etc.). Please contact the lab for questions or information.

Testing Methods

  • Flow Cytometry: Peripheral blood mononuclear cells (PBMCs) are evaluated by multiparameter flow cytometry for cell surface expression of CD4 and CD25 as well as intracellular FOXP3.
  • Gene Sequencing: All exons (-1 to 11) and the polyadenylation site are evaluated by bidirectional sequencing from genomic DNA. Sequencing includes all exon/intron boundaries.

CPT Codes for Testing

  • Flow Cytometry: 83907(1), 88184(1), 88185(2), 83912(1)
  • FOXP3 Gene Sequencing: 83907(1), 83981(1), 83898(13), 83894(13), 83904(26), 83912(1)
  • CD25 Gene Sequencing: 83907(1), 83981(1), 83898(8), 83894(8), 83904(16), 83912(1)
  • STAT5B Gene Sequencing: 83907(1), 83981(1), 83898(19), 83894(19), 83904(38), 83912(1)

Turnaround Times

  • Flow Cytometry: 5 business days from receipt of sample.
  • Gene Sequencing: FOXP3 — 4 weeks from receipt of sample; CD25 and STAT5B — 6 weeks from receipt of sample.

Testing Forms for IPEX Syndrome

Sample Submission Form, Available Tests and Sample Requirements/Shipping Instructions (PDF)

See Also

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