原標(biāo)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(yīng)答
——浙大迪迅 譯
?、俦尘埃郝员歉]炎合并鼻息肉(CRSwNP)的特點(diǎn)是局部產(chǎn)生多克隆IgE亞型。雖然組織IgE的濃度可以達(dá)到幾千KU/L,但是對(duì)于IgE介導(dǎo)的炎癥在鼻息肉患者中的調(diào)控機(jī)制還不是很清楚。②方法:我們?cè)噲D確定鼻息肉患者局部誘導(dǎo)的IgG抗體是否能夠抑制IgE介導(dǎo)的促過敏反應(yīng)。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(duì)照組的鼻腔息肉勻漿。采用免疫固相變應(yīng)原芯片法測(cè)定IgE水平。我們?cè)u(píng)估了含有IgE 的鼻息肉勻漿(有或無IgG消耗)在促進(jìn)IgE誘導(dǎo)的過敏原表達(dá)、嗜堿性細(xì)胞活化和組胺釋放方面的能力。采用免疫球蛋白454測(cè)序法評(píng)價(jià)局部IgE和IgG譜。③結(jié)果:我們發(fā)現(xiàn)IgG在控制鼻息肉患者的IgE介導(dǎo)的炎癥反應(yīng)中起著關(guān)鍵作用。損耗鼻勻漿中的IgG,導(dǎo)致了 IgE-誘導(dǎo)的CD23-介導(dǎo)的過敏原與B細(xì)胞的結(jié)合量的增加,也增強(qiáng)FcεRI-介導(dǎo)的過敏原-驅(qū)動(dòng)的嗜堿細(xì)胞激活和組胺釋放。對(duì)金黃色葡萄球菌腸毒素特異性IgE抗體也有類似的反應(yīng)。鼻息肉中IgG抑制IgE介導(dǎo)的炎癥的能力是基于這樣一個(gè)事實(shí),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(diǎn)。④結(jié)論:CRSwNP患者多克隆IgE亞型具有功能性,可促進(jìn)IgE介導(dǎo)的過敏性炎癥反應(yīng),并可被相應(yīng)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(shí)交流平臺(tái),為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。