Abstract 618: Hypoxia Inducible Factor 1a Stabilization in Autosomal Dominant Hyper IgE Syndrome Fibroblasts Rescues Impaired Ability to Support Angiogenesis

Background: Autosomal dominant Hyper-IgE syndrome (AD-HIES) is a rare primary immunodeficiency caused by dominant negative mutations in signal transducer and activator of transcription 3 (STAT3), a mediator of widespread physiological processes. It is characterized by dermatitis, recurrent infections, elevated IgE, poor post-surgical healing, and connective tissue abnormalities. How STAT3 deficiency leads to this phenotype, however, is not known. Current treatment options are limited to antimicrobials for infection control. The aim of this study was to investigate which of STAT3’s many functions are dis-regulated in AD-HIES, and where potential targets for therapy may lie. Methods: We used skin fibroblasts (SF) from 3 AD-HIES patients and 3 normal volunteers. To evaluate potentially affected pathways, we utilized RNA- Seq and subsequent Gene Set Enrichment (GSEA) and pathway analysis (Pathway Studio, GeneGo Metacore). Endothelial cell tube formation assay was used to assess ability of AD-HIES SFs to suppo...