These include defects in the IFN-γ/STAT1 signaling pathway (including gain-of-function STAT1 related diseases), elevated levels of serum anti-IFN-γ neutralizing autoantibodies (or adult-onset immunodeficiency syndrome; AOID), STAT3 Hyper IgE syndrome, mutations in the CD40 ligand (CD40L or CD154) gene, X-linked hyper-IgM syndrome, malignancy and targeted therapy for anti-cancer (11). Here, CD40LG is linked to acquired adult-onset immunodeficiency.