Disturbances in serum immunoglobulin values, especially increased IgM, normal or decreased IgG with low IgG2, or disturbed humoral post-vaccination response warrant lymphocyte immunophenotyping in search for the typical CD4 and CD8 naïve T-cell lymphopenia, increased transitional B cells and activation of CD8 T cells associated with APDS. The gene discussed is CD40LG; the disease is activated PI3K-delta syndrome.