The Hyper-IgE Syndromes: Lessons in Nature, From Bench to Bedside.

: Hyper-IgE syndrome is a primary immunodeficiency marked by abnormalities in the coordination of cell-cell signaling with the potential to affect TH17 cell, B cell, and neutrophil responses. Clinical manifestations include recurrent skin and lung infections, serum IgE elevation, connective tissue repair and development alterations, and the propensity for vascular abnormalities and tumor development. Signal transducer and activator of transcription 3 (STAT3) signaling, dedicator of cytokinesis 8 (DOCK8) signaling, and tyrosine kinase 2 (TYK2) signaling alterations have been implicated in 3 forms of hyper-IgE syndrome.

Interleukin-13 signaling and its role in asthma.

Asthma affects nearly 300 million people worldwide. The majority respond to inhaled corticosteroid treatment with or without beta-adrenergic agonists. However, a subset of 5 to 10% with severe asthma do not respond optimally to these medications. Different phenotypes of asthma may explain why current therapies show limited benefits in subgroups of patients. Interleukin-13 is implicated as a central regulator in IgE synthesis, mucus hypersecretion, airway hyperresponsiveness, and fibrosis. Promising research suggests that the interleukin-13 pathway may be an important target in the treatment of the different asthma phenotypes.