Key Clinical and Laboratory Features

  • Common clinical features: IPEX-like symptoms including infant-onset chronic diarrhea with villus atrophy, endocrinopathies (Type 1 diabetes, thyroiditis) and dermatitis (eczema, pemphigus nodularis, psoriasiform dermatitis) are almost universal. Hepatosplenomegaly, lymphadenopathy and lymphocytic infiltrates in lung, gut and liver are also common. Chronic, severe viral infections (particularly CMV) are present in almost all patients.
  • Other clinical features: Persistent thrush/candidiasis, recurrent bacterial infections, EBV infections, etc.
  • Physical exam: Dermatitis, chronic cutaneous Candida infections
  • Common laboratory features: Moderate T-cell lymphopenia, poor T-cell proliferative response to mitogenic stimuli, IgE normal to mildly elevated

Testing Approach

 TESTCOMMENTS
GENE CD25 (IL2RA) Gene Sequencing   The gold standard for confirming a diagnosis of CD25 (IL2RA) deficiency in a patient with symptoms and absent CD25 expression.
PROTEIN FOXP3/CD25 Protein Flow/TREGFlow   Few CD25-deficient patients are described but all lack CD25 protein expression on the surface of T cells. The protein test is estimated to be at least 90% sensitive to detect affected patients.
FUNCTION X-SCID Screen by Flow(pSTAT3/5) CD25 (α chain of the IL-2 receptor), when combined with the β and γ chains, creates the high-affinity receptor for IL-2. The function of the CD25 chain can therefore be evaluated by stimulating T cells with low vs. high-dose IL-2 and determining whether the STAT5 transcription factor is phosphorylated normally on tyrosine. This test is performed as part of the X-SCID Screen by Flow and would be recommended in the rare situation where a mutation is identified in CD25 but the protein is still expressed.
OTHER
 
  • Lymphocyte subset analysis: T-cell lymphopenia is common in patients.
  • Lymphocyte proliferation to mitogens: Patient T cells often do not proliferate well to mitogens. This process is highly dependent on IL-2 but patient T cells are much less sensitive to IL-2 stimulation because they lack the IL2RA receptor chain.
  • IgE level: Normal to mildly elevated.