原標題:慢性鼻竇炎合并鼻息肉患者廣泛的IgG譜可調(diào)節(jié)促炎IgE應答
——浙大迪迅 譯
?、俦尘埃郝员歉]炎合并鼻息肉(CRSwNP)的特點是局部產(chǎn)生多克隆IgE亞型。雖然組織IgE的濃度可以達到幾千KU/L,但是對于IgE介導的炎癥在鼻息肉患者中的調(diào)控機制還不是很清楚。②方法:我們試圖確定鼻息肉患者局部誘導的IgG抗體是否能夠抑制IgE介導的促過敏反應。收集花粉過敏的慢性鼻竇炎合并鼻息肉(CRSwNP)患者和非過敏對照組的鼻腔息肉勻漿。采用免疫固相變應原芯片法測定IgE水平。我們評估了含有IgE 的鼻息肉勻漿(有或無IgG消耗)在促進IgE誘導的過敏原表達、嗜堿性細胞活化和組胺釋放方面的能力。采用免疫球蛋白454測序法評價局部IgE和IgG譜。③結果:我們發(fā)現(xiàn)IgG在控制鼻息肉患者的IgE介導的炎癥反應中起著關鍵作用。損耗鼻勻漿中的IgG,導致了 IgE-誘導的CD23-介導的過敏原與B細胞的結合量的增加,也增強FcεRI-介導的過敏原-驅(qū)動的嗜堿細胞激活和組胺釋放。對金黃色葡萄球菌腸毒素特異性IgE抗體也有類似的反應。鼻息肉中IgG抑制IgE介導的炎癥的能力是基于這樣一個事實,即在過敏和非過敏受試者中,IgG與IgE譜之間存在廣泛的共享抗原靶點。④結論:CRSwNP患者多克隆IgE亞型具有功能性,可促進IgE介導的過敏性炎癥反應,并可被相應的IgG亞型部分拮抗。這很可能是由于IgE和IgG在鼻息肉患者中存在廣泛共享的克隆型。
延伸閱讀
JACI
[IF:13.1]
Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses
DOI: https://doi.org/10.1016/j.jaci.2019.02.001
Abstract:
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by local production of polyclonal IgE idiotypes. Although tissue IgE concentrations can be in the range of several thousand kilounits per liter, the regulatory mechanisms by which IgE-mediated inflammation is controlled in patients with nasal polyps are not well understood.
Objective
We sought to determine whether locally induced IgG antibodies in patients with nasal polyps can inhibit an IgE-mediated proallergic response.
Methods
Nasal polyp homogenates were collected from patients with grass pollen allergy with CRSwNP and nonallergic control subjects. IgE levels were measured using the Immuno Solid-phase Allergen Chip assay. IgE-containing nasal polyp homogenates with or without IgG depletion were evaluated for their capacity to promote IgE-facilitated allergen presentation, basophil activation, and histamine release. Local IgE and IgG repertoires were evaluated using Immunoglobulin 454 sequencing.
Results
We show that IgG plays a key role in controlling IgE-mediated inflammatory responses in patients with nasal polyps. Depletion of IgG from nasal homogenates resulted in an increase in CD23-mediated IgE-facilitated allergen binding to B cells but also enhanced FcεRI-mediated allergen-driven basophil activation and histamine release. A similar response was observed in relation to specific IgE antibodies to Staphylococcus aureus enterotoxins. The capacity of IgG in nasal polyps to limit IgE-mediated inflammation is based on the fact that IgG repertoires widely share the antigen targets with the IgE repertoires in both allergic and nonallergic subjects.
Conclusion
Polyclonal IgE idiotypes in patients with CRSwNP are functional, promote IgE-mediated proallergic inflammation, and are partially antagonized by corresponding IgG idiotypes. This is most likely due to the fact that IgE and IgG clonotypes are widely shared in patients with nasal polyps.
All Authors:
Mohamed H. Shamji Irene Thomsen Janice A. Layhadi Jasper Kappen Gabri?le Holtappels Umit Sahiner Amy Switzer Stephen R. Durham Oliver Pabst
Claus Bachert?
2019-5-6 Article
創(chuàng)建過敏性疾病的科研、科普知識交流平臺,為過敏患者提供專業(yè)診斷、治療、預防的共享平臺。