For the first time, our in vitro data suggest that the exaggerated but ineffective upregulation of type 1 interferon–mediated defense observed in patients with AE12 might reflect an inherent defect downstream of FLG rather than/in addition to a deregulated response to pathogen exposure.12, 53 Therefore dysregulation of these pathways as a result of inherited or acquired FLG deficiency might contribute to the propensity of patients with AE to have bacterial and viral skin infections. This evidence concerns the gene FLG and hyperinsulinemic hypoglycemia, familial, 4.