Table 3.

Laboratory investigations in STAT3-HIES

Investigation	Comments
Full blood count	Eosinophilia in 70% Occasionally, anemia and/or neutropenia [3, 25]
Lymphocyte subsets	Total lymphocyte count is normal Reduced memory CD19 + CD27 + B-lymphocytes in 90% [3, 31, 132] Reduced memory T-lymphocytes [34]
Immunoglobulins	Total IgA, IgM, IgG normal Specific IgG to recall antigens is reduced Raised IgE, usually > 1000 IU/ml, which peaks in infancy and may normalize in adulthood [13]
Specialist immunophenotyping	Absent IL-17-producing Th17-lymphocytes Current strategies for identification of Th17-lymphocytes include the CD4 + CD45RA-CXCR5-CCR6 + T-lymphocyte phenotype [133, 134] or ex vivo staining for IL-17A following stimulation or induction of differentiation of naïve CD4 + T-lymphocytes [3]
Molecular analysis of STAT3	Heterozygous mutations are typically missense or short in-frame deletions; identification of new variants is complicated by dominant-negative and gain-of-function mutations sharing the same codon [3, 103] Any identified variant should be confirmed to be deleterious prior to attributing pathogenicity Panels may include other candidate genes for HIES, e.g., PGM3, IL6ST, and ZNF341 (which is a recessive phenocopy of STAT3-HIES), or DOCK8 (a combined immunodeficiency sharing features with HIES)