TNF and activated PI3K-delta syndrome: The elucidation of molecular drivers of IEI has important consequences towards the management of these patients since it can rationalize targeted treatment (eg. JAK-inhibition in interferonopathies, TNF-α inhibitors in DADA2, CTLA4 agonists in CTLA4 haploinsufficiency, sirolimus in ALPS, leniolisib in APDS), bone marrow transplant in some cases, provide prognostic information and inform genetic counselling.