Ingested allergens must be absorbed systemically to induce systemic anaphylaxis

Background: IgE-mediated food allergy is a common cause of enteric disease and is responsible for approximately 100 systemic anaphylaxis deaths in the United States each year. IgG antibodies can protect against IgE-mediated systemic anaphylaxis induced by injected antigens by neutralizing antigens before they can bind to mast cell-associated IgE. Objective: We have investigated whether IgA and IgG antibodies can similarly protect against systemic, IgE-mediated anaphylaxis induced by ingested antigens and, if so, whether IgA and IgG antibodies protect by neutralizing antigens before or after their systemic absorption. Methods: Murine passive and active anaphylaxis models were used to study the abilities of serum versus gut lumenal IgA antibodies and serum IgG antibodies to inhibit systemic anaphylaxis induced by ingested allergens in normal mice, mice deficient in the ability to secrete IgA into the intestines, and mice in which intestinal IL-9 overexpression has induced intestinal mastocytosis and increased intestinal permeability. Results: IgE-mediated systemic anaphylaxis and mast cell degranulation induced by antigen ingestion are suppressed by both serum antigen-specific IgA and IgG, but not by IgA within the gut lumen. Conclusion: Systemic rather than enteric antibodies protect against systemic anaphylaxis induced by ingested antigen. This implies that ingested antigens must be absorbed systemically to induce anaphylaxis and suggests that immunization protocols that increase serum levels of antigen-specific, non-IgE antibodies should protect against severe food allergy. (J Allergy Clin Immunol 2011;127:982-9.)