Furthermore, a recently described immune deficiency in humans, the activated PI3K-δ syndrome (APDS) (e.g., several point mutations occur in the p110δ catalytic domain, leading to exaggerated PI3K-δ signaling), clearly demonstrates the clinical outcomes associated with aberrant activation of PI3K-δ, including recurrent respiratory infections, airway damage and the extremely high incidence of bronchiectasis, and dysfunctional T and B lymphocytes, all of which highlight the critical role of this isoform, particularly in the respiratory system [17,18]. This evidence concerns the gene PIK3CD and Down syndrome.