Anaphylaxis to Peanuts is Mediated by IgE
Peanut anaphylaxis is primarily an IgE-mediated type I hypersensitivity reaction, not mediated by complement or immune complexes. 1, 2
Mechanism of Peanut Anaphylaxis
The allergic response to peanuts occurs through the classical IgE pathway:
Peanut-specific IgE antibodies bind to high-affinity receptors (FcεRI) on mast cells and basophils, and upon re-exposure to peanut allergens (particularly Ara h 2, the most anaphylactic peanut protein), cross-linking of IgE triggers cellular degranulation and release of histamine and other mediators 1, 3, 4
Clinical anaphylaxis manifests as cutaneous, respiratory, cardiovascular, and gastrointestinal symptoms occurring singly or in combination, representing the classic features of type I, IgE-mediated hypersensitivity 2
Gene therapy targeting IgE (AAVrh.10anti-hIgE) blocks anaphylaxis scores, death from anaphylaxis, and peanut-induced histamine release in humanized mouse models, confirming the central role of IgE in mediating these reactions 1, 5
Evidence from Transplant Medicine Confirms IgE Mechanism
Real-world human evidence from solid organ transplantation provides compelling proof:
Transfer of peanut allergy occurs when donor-specific IgE (particularly to Ara h 1,2,3, and 6) is transferred to recipients, resulting in clinical anaphylaxis upon peanut exposure 1
Recipients who received organs from donors with peanut allergy developed anaphylaxis (urticaria, acute asthma, stomach pain, vomiting, dyspnea) when exposed to peanuts, with detectable peanut-specific IgE in their sera 1, 6
Standard immunosuppression does not prevent IgE-mediated reactions, demonstrating that the IgE pathway operates independently of T-cell suppression 1, 6
Multiple Pathways Contribute But IgE Dominates
While IgE is the primary mediator, complete understanding requires acknowledging contributory mechanisms:
IgG1 antibodies and phagocytes (macrophages) contribute to the full spectrum of severe anaphylactic reactions, as demonstrated in mouse models where combined deficiency of mast cells and phagocytes (but not mast cells and basophils alone) prevented nearly all clinical signs 7
However, IgE remains the dominant pathway as evidenced by the effectiveness of anti-IgE therapies (omalizumab and gene therapy) in preventing anaphylaxis 1, 5
Complement and immune complexes are not primary mediators of peanut anaphylaxis, though IgG1-mediated pathways may involve some complement activation as a secondary phenomenon 7
Clinical Implications
Diagnosis relies on detecting peanut-specific IgE through skin prick testing and serum IgE measurements, particularly to recombinant allergens Ara h 1,2,3, and 6 1
Treatment strategies target the IgE pathway, including anti-IgE monoclonal antibodies, oral immunotherapy aimed at reducing IgE responses, and emergency epinephrine for acute reactions 1, 6
The TSLP-basophil-IL-4 axis drives IgE-mediated food allergy development through IL-4, representing upstream targets for intervention 1