While venom-specific IgE has been commonly associated with the risk of allergy and anaphylaxis, the alternative toxin hypothesis (originally postulated by Margie Profet) suggested a beneficial function of IgEs in host defense against noxious substances, for instance by increasing the innate detoxifying potential of MCs.8,9 The results of our laboratory17,18 and the Medzhitov19 laboratory provided evidence for this idea; however, the specific molecular consequences of IgE sensitization on MC responses to venoms have not been fully addressed. The gene discussed is IGHE; the disease is anaphylaxis.