Peanuts can contribute to anaphylactic shock by activating complement

BackgroundPeanut allergy is the most common food-related cause of lethal anaphylaxis and, unlike other food allergies, typically persists into adulthood. Resistance to digestion and dendritic cell activation by the major peanut allergen Ara h 1 are reported to contribute to its allergenicity.ObjectiveWe sought to evaluate whether peanut molecules might also promote anaphylaxis through an innate immune mechanism.MethodsNaive mice were treated with a β-adrenergic receptor antagonist and long-acting IL-4 to increase sensitivity to vasoactive mediators and injected with peanut extract (PE). Shock was detected and quantified by means of rectal thermometry. Gene-deficient mice and specific antagonists were used to determine the roles of specific cell types, complement, Fc receptors, and vasoactive mediators in shock pathogenesis.ResultsPE induces dose-dependent shock. PE activates complement in vivo in mice and in vitro in mice and human subjects. C3a and, to a lesser extent, stimulatory immunoglobulin receptors contribute to PE-induced shock. PE-induced shock depends more on macrophages and basophils than on mast cells. Platelet-activating factor and, to a lesser extent, histamine contribute to PE-induced shock. PE induces shock in the absence of the adaptive immune system. LPS contamination is not responsible for PE-induced shock. PE and IgE-mediated mast cell degranulation synergistically induce shock. Tree nuts have similar effects to PE, and skim milk and egg white do not.ConclusionPeanuts can contribute to shock by causing production of C3a, which stimulates macrophages, basophils, and mast cells to produce platelet-activating factor and histamine.