SPPL2A and Alzheimer disease: In patients with Interferon Regulator Factor (IRF) eight mutations the AR variant causes a complete lack of circulating monocytes and DCs, while the AD variant associates with a selective depletion of CD11c+CD1c+ circulating dendritic cells (18, 19), as reported also in patients with the recently described SPPL2A (signal peptide peptidase-like 2A) deficiency, where a defective IL-12 and IL-23 production by mDCs may disrupt the priming of T lymphocytes (19, 20).