Pulmonary Vascular Leak Requires IgE during Respiratory Viral Infection
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Brian T. Kelly, MD MA, Jennifer L Santoro, BS, Mitchell H. Grayson, MD FAAAAI

Severe respiratory viral infections during childhood have been associated with significantly increased risk of asthma. Infection with the paramyxovirusSendai virus (SeV) leads to development of post-viral asthma in mice.  Essential to this pathway is production of anti-viral IgE.   Removal of IgE in humans resulted in reduced asthma exacerbations in a clinical trial.  The role of IgE in the acute anti-viral immune response is unknown; we, therefore, hypothesized that IgE is essential for induction of pulmonary vascular leak during a respiratory viral infection.


C57BL6 (WT) or IgE–/– mice were inoculated with SeV.  One group of IgE–/– mice received 3mcg anti-ova IgE on day 5 post inoculation (PI) SeV followed 1 day later with 10mcg of OVA intranasally.  On day 8 PI, Evans Blue Dye (EBD; binds albumin to quantify vascular leak) was given intravenously, and 1 hour later pulmonary vasculature flushed with PBS, and EBD concentration in lung homogenates determined by spectrophotometry. EBD extravasation in lung after viral infection was compared to uninfected WT and IgE–/–mice (Fold EBD).


As measured by fold EBD, WT mice developed vascular leak, which was completely abrogated in IgE–/– mice (3.43±0.18 v. 1.26±0.20, mean±SEM fold EBD concentration, WT v. IgE–/–, p<0.0001, n>4).  Administration of IgE and antigen to IgE–/– mice restored vascular leak (3.31±0.08, p=0.54 v. WT;  p<0.0001 v. IgE–/–alone, n>4).


IgE is required for development of pulmonary vascular leak during a severe respiratory viral infection.  Ongoing projects will identify the cell(s) responsible for the leak.