Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.
Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.
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DOI：
10.1016/j.jaci.2016.06.066
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Gould HJ
中科院分区：
文献类型：
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作者：
Chen JB;James LK;Davies AM;Wu YB;Rimmer J;Lund VJ;Chen JH;McDonnell JM;Chan YC;Hutchins GH;Chang TW;Sutton BJ;Kariyawasam HH;Gould HJ
慢性鼻窦炎伴鼻息肉与局部免疫球蛋白过度生成和存在抗金黄色葡萄球菌肠毒素（SAE）的IgE抗体有关。阿司匹林加重的呼吸道疾病是一种严重的慢性鼻窦炎伴鼻息肉，几乎所有患者都表达抗SAE。我们的目的是了解抗体反应的严重不良事件，并确定他们是否承认严重不良事件通过其互补决定区（CDR）或框架区。应用荧光激活细胞分选技术，用标记的葡萄球菌肠毒素（SE）A、SED和SEE从3例阿司匹林致呼吸道疾病患者鼻息肉中分离出单一的SAE特异性B细胞。将具有“匹配的”重链和轻链的重组抗体克隆为IgG 1，并将通过ELISA和表面等离子体共振测定的对特定SAE具有高亲和力的重组抗体重新克隆为IgE和抗原结合片段。在嗜碱性粒细胞脱粒测定中测试IgE活性。分离37个SAE特异性、IgG或IgA表达的B细胞，并产生6个抗SAE克隆，SEA、SED和SEE各2个。竞争结合试验表明，抗SEE抗体识别SEE中的非重叠表位。出乎意料的是，每个抗SEE介导的SE诱导的嗜碱性粒细胞脱粒，和IgG 1或抗原结合片段的每个抗SEE增强脱粒的其他抗SEE。SEE可通过同时以常规方式作为抗原与CDR结合以及作为超抗原与抗SEE IgE-FcεRI复合物中抗SEE IgE的框架区结合来激活嗜碱性粒细胞。抗SEE IgG 1可通过CDR作为常规抗体增强抗SEE IgE的活性，或同时作为常规抗体和“超级抗体”通过CDR和框架区增强抗SEE IgE-Fc εRI复合物中SEE的活性。
Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with “matched” heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as “superantibodies” through CDRs and framework regions to SEEs in SEE–anti-SEE IgE-FcεRI complexes.