Blockade of peanut allergy with a novel Ara h 2–Fcγ fusion protein in mice - 27/12/12
, Yongtao Sun, MD, PhD b, ⁎ 
, Lee-Jah Chang, MD a, Newton Li, MD a, Huabin Li, MD, PhD a, Yanni Yu, BSc a, Paul J. Bryce, PhD a, Leslie C. Grammer, MD a, Robert P. Schleimer, PhD a, Daocheng Zhu, MD, PhD a, b, ⁎ Corresponding author: Daocheng Zhu, MD, PhD, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, 240 E Huron, Chicago, IL 60611.Yongtao Sun.Abstract |
Background |
Conventional immunotherapy for peanut allergy using crude peanut extracts is not recommended because of the unacceptably high risk of anaphylaxis. Allergen-specific immunotherapy is not currently undertaken for peanut allergy.
Objectives |
The objective of this study was to develop a novel peanut-human fusion protein to block peanut-induced anaphylaxis.
Methods |
We genetically designed and expressed a novel plant-human fusion protein composed of the major peanut allergen Ara h 2 and human IgG Fcγ1. We tested the Ara h 2–Fcγ fusion protein (AHG2)’s function in purified human basophils. Transgenic mice expressing human FcεRI⍺ and a murine peanut allergy model were used.
Results |
AHG2 inhibited histamine release induced by whole peanut extract (WPE) from basophils of patients with peanut allergy, whereas the fusion protein itself did not induce mediator release. AHG2 inhibited the WPE-induced, peanut-specific, IgE-mediated passive cutaneous anaphylaxis in hFcεRI⍺ transgenic mice. AHG2 also significantly inhibited acute anaphylactic reactivity, including the prototypical decrease in body temperature in WPE-sensitized mice challenged with crude peanut extract. Histologic evaluation of the airways showed that AHG2 decreased peanut-induced inflammation, whereas the fusion protein itself did not induce airway inflammation in peanut-sensitized mice. AHG2 did not exert an inhibitory effect in mice lacking FcγRII.
Conclusion |
AHG2 inhibited peanut-specific IgE-mediated allergic reactions in vitro and in vivo. Linking specific peanut allergen to Fcγ can provide a new approach for the allergen immunotherapy of peanut allergy.
El texto completo de este artículo está disponible en PDF.Key words : Food allergy, peanut, fusion protein, immunotherapy, anaphylaxis, mast cells, basophils
Abbreviations used : AHG2, NP, PCA, SCIT, WPE
Esquema
| Supported by National Institutes of Health grant R21 AI088808; the Food Allergy and Anaphylaxis Network; the American Academy of Allergy, Asthma & Immunology; the Northwestern Memorial Foundation; and the Food Allergy Initiative. |
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| Disclosure of potential conflict of interest: D. Zhu has received grants and travel support from the National Institutes of Health (NIH); the Food Allergy and Anaphylaxis Network; the American Academy of Allergy, Asthma & Immunology (AAAAI); the Northwestern Memorial Foundation; and the Food Allergy Initiative. L. C. Grammer has received grants and travel support from the NIH, the Food Allergy and Anaphylaxis Network, and S&C Electric Co; has consultant arrangements with Astellas Pharmaceuticals; is employed by Northwestern University and the Northwestern Medical Faculty Foundation; has received payment for lectures from the AAAAI; and has received royalties from Lippincott and UpToDate. R. P. Schleimer has received grants from the NIH and has consultant arrangements with Intersect ENT, GlaxoSmithKline, and Allakos. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 1
P. 213 - janvier 2013 Regresar al número
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