IGHE and Immunodeficiency: In humans, autosomal-dominant (AD) hyper-IgE syndrome (HIES), caused by dominant-negative STAT3 mutations, is a complex immunodeficiency that presents with pneumonia, lung abnormalities, high levels of IgE, eosinophilia, eczema, and skeletal and connective tissue abnormalities including retained primary teeth, scoliosis, and craniosynostosis (Smithwick et al., 1978; Höger et al., 1985; Gahr et al., 1987; Grimbacher et al., 1999a, 2005; Holland et al., 2007; Minegishi et al., 2007; Miller et al., 2017).