Oral immunotherapy induces IgG antibodies that act through Fc?RIIb to suppress IgE-mediated hypersensitivity - 05/12/14
Abstract |
Background |
Food-induced anaphylaxis is triggered by specific IgE antibodies. Paradoxically, some subjects with significant IgE levels can ingest allergenic foods without incident. Similarly, subjects completing oral immunotherapy (OIT) tolerate food challenges despite persistent high-titer food-specific IgE.
Objective |
We sought to test whether IgG antibodies induced by food immunotherapy prevent food-induced anaphylaxis and whether this occurs through the inhibitory receptor FcγRIIb.
Methods |
Food allergy–susceptible Il4raF709 mice were enterally sensitized to ovalbumin (OVA). Similarly sensitized IgE-deficient (IgE−/−) Il4raF709 mice, which can ingest OVA without anaphylaxis, were subjected to a high-dose enteral OVA desensitization protocol (OIT). Sera from both groups were tested for the ability to activate or inhibit bone marrow mast cells (BMMCs) exposed to allergen or to passively transfer allergy to naive hosts. In parallel experiments sera obtained from patients with peanut allergy before and after undergoing OIT were interrogated for their ability to enhance or suppress peanut-induced activation in an indirect assay by using basophils from nonallergic donors.
Results |
Il4raF709 mice exhibited strong OVA-specific IgE responses. Their sera efficiently sensitized BMMCs for activation by antigen challenge. Sera from Il4raF709/IgE−/− mice subjected to OVA OIT suppressed BMMC responses. This inhibition was IgG mediated and FcγRIIb dependent. Similarly, pre-OIT but not post-OIT sera from patients efficiently sensitized basophils for peanut-induced activation. IgG antibodies in post-OIT sera suppressed basophil activation by pre-OIT sera. This inhibition was blocked by antibodies against FcγRII.
Conclusion |
Food-specific IgG antibodies, such as those induced during OIT, inhibit IgE-mediated reactions. Strategies that favor IgG responses might prove useful in the management of food allergy.
Le texte complet de cet article est disponible en PDF.Key words : Food allergy, tolerance, anaphylaxis, IgE, desensitization, oral immunotherapy
Abbreviations used : BMMC, LAMP-1, OD, OIT, OVA, SCIT, TNP
Plan
| Supported by National Institutes of Health grants NIAID R56 AI100889 (to H.C.O.), 5T32AI007512-24 (to O.T.B., S.L.L., and J.S.Z.), and UL1 RR 025758 (to D.T.U.) and by grants from the Thrasher Foundation (to D.T.U.), the Bunning Food Allergy Project (to D.T.U., H.C.O., and R.R.), the Jasmine and Paul Mashikian Fund (to D.T.U.), Genentech (to D.T.U.), Consejo Nacional de Ciencia y Tecnología (CONACyT) grant 207999 (to J.M.-T.), and the Department of Defense: DOD 11-1-0553 (to T.A.C.). |
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| Disclosure of potential conflict of interest: O. T. Burton and S. L. Logsdon have received research support and travel support from the National Institutes of Health (NIAID R56 AI100889, 5T32AI007512-24, and UL1 RR 025758). T. A. Chatila has received research support from the National Institutes of Health and the Department of Defense (DOD 11-1-0553). L. C. Schneider has received research support from the Thrasher Foundation and Genentech and is a board member for Food Allergy Research and Education. R. Rachid has received research support from the Bunning Food Allergy Project, the Jasmine and Paul Mashikian Fund, Food Allergy Research and Education, the Allergen Research Corporation, and CSL Behring and has received an honorarium from Baxter. D. T. Umetsu has received research support from the Thrasher Foundation, Genentech, and Food Allergy Research and Education; is employed by and has stock/stock options in Genentech; and has received royalties from Boston Children's Hospital and Stanford University. H. C. Oettgen has received research support from the National Institutes of Health and the Bunning Food Allergy Project. |
Vol 134 - N° 6
P. 1310 - décembre 2014 Retour au numéro
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