Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE-mediated hypersensitivity.
Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE-mediated hypersensitivity.
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DOI：
10.1016/j.jaci.2014.05.042
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发表时间：
2014-12
影响因子：
14.2
通讯作者：
Oettgen, Hans C.
中科院分区：
文献类型：
--
作者：
Burton, Oliver T.;Logsdon, Stephanie L.;Zhou, Joseph S.;Medina-Tamayo, Jaciel;Abdel-Gadir, Azza;Noval Rivas, Magali;Koleoglou, Kyle J.;Chatila, Talal A.;Schneider, Lynda C.;Rachid, Rima;Umetsu, Dale T.;Oettgen, Hans C.
食物过敏反应是由特异性IgE抗体引发的。奇怪的是，一些具有显著IgE水平的个体可以摄入过敏性食物而不会发生意外。类似地，完成口服免疫疗法（OIT）的受试者耐受食物激发，尽管持续存在高滴度食物特异性IgE。检测食物免疫疗法诱导的IgG抗体是否可预防食物诱导的过敏反应，以及这是否通过抑制性受体FcγRIIb发生。食物过敏敏感的Il 4 raF 709小鼠对卵清蛋白（OVA）进行肠内致敏。同样致敏的IgE缺陷型Il 4 raF 709/IgE−/−小鼠可以摄入OVA而不会发生过敏反应，对这些小鼠进行高剂量肠内OVA脱敏方案（OIT）。检测两组血清激活或抑制暴露于过敏原的骨髓肥大细胞（BMMC）的能力，或被动将过敏传递给幼稚宿主的能力。在平行实验中，在使用来自非过敏供体的嗜碱性粒细胞的间接测定中，询问在经历OIT之前和之后从花生过敏患者获得的血清增强或抑制花生诱导的活化的能力。Il 4 raF 709小鼠表现出强烈的OVA特异性IgE应答。它们的血清通过抗原攻击有效地致敏BMMC活化。来自经受OVA OIT的Il 4 raF 709/IgE−/−小鼠的血清抑制BMMC应答。这种抑制作用是IgG介导的和Fcγ RIIb依赖性的。同样，OIT前，但不是OIT后的患者血清有效地致敏嗜碱性粒细胞花生诱导的激活。OIT后血清中的IgG抗体抑制了OIT前血清对嗜碱性粒细胞的激活。这种抑制作用可被抗FcγRII抗体阻断。食物特异性IgG抗体，如OIT期间诱导的抗体，可抑制IgE介导的反应。有利于IgG反应的策略可能在食物过敏的管理中是有用的。
Food anaphylaxis is triggered by specific IgE antibodies. Paradoxically, some individuals 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. To test whether IgG antibodies induced by food immunotherapy prevent food-induced anaphylaxis, and whether this occurs via the inhibitory receptor FcγRIIb. Food allergy-susceptible Il4raF709 mice were enterally sensitized to ovalbumin (OVA). Similarly sensitized IgE-deficient Il4raF709/IgE−/− 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 (BMMC) exposed to allergen, or to passively transfer allergy to naïve hosts. In parallel experiments, sera obtained from peanut allergic patients before and after undergoing OIT were interrogated for their ability to enhance or suppress peanut-induced activation in an indirect assay using basophils from non-allergic donors. Il4raF709 mice exhibited strong OVA-specific IgE responses. Their sera efficiently sensitized BMMC 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. 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.
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牛奶过敏的早期恢复与IgE降低并增加IgG4与牛奶表位的结合有关。
影响因子：
14.2
作者：
Savilahti, Emma M.;Rantanen, Ville;Lin, Jing S.;Karinen, Sirkku;Saarinen, Kristiina M.;Goldis, Marina;Makela, Mika J.;Hautaniemi, Sampsa;Savilahti, Erkki;Sampson, Hugh A.
通讯作者：
Sampson, Hugh A.
DOI：
10.1084/jem.20101757
发表时间：
2011-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Föger N;Jenckel A;Orinska Z;Lee KH;Chan AC;Bulfone-Paus S
通讯作者：
Bulfone-Paus S
影响因子：
2.6
作者：
Caubet, Jean-Christoph;Sampson, Hugh A.
通讯作者：
Sampson, Hugh A.
影响因子：
5.1
作者：
JAMES, JM;SAMPSON, HA
通讯作者：
SAMPSON, HA
影响因子：
14.2
作者：
Liu, Yu;Sun, Yongtao;Zhu, Daocheng
通讯作者：
Zhu, Daocheng