Whilst dominant negative mutations in signal transduction and activator of transcription (STAT) 3 cause a complex multisystem immunodeficiency with recurrent staphylococcal and fungal infection, eczema, and connective tissue disease (STAT3 hyper IgE syndrome) (117, 118), germline activating mutations lead to exaggerated transcriptional activity of STAT3 and impaired signaling through the other STAT molecules (20). This evidence concerns the gene STAT3 and immunodeficiency disease.