摘要
哮喘患儿IgE谱反映了一种自适应的B细胞反应,说明抗原驱动的选择。然而,这可能不适用于过敏性皮炎,过敏性皮炎往往是过敏性疾病的第一表现。本研究的目的是描述患有特应性皮炎的学龄前儿童的IgE谱,关于超抗原激活的迹象、克隆的关系,Ag选择的适应证。总RNA从5例特应性皮炎儿童的PBMCs中提取总RNA。IgE转录子用RT-PCR进行扩增、克隆和测序。我们获得了200个功能性IgE序列,这与从11例哮喘儿童中获得了1140个功能性IgE序列相比较。而哮喘基因的H Ig链可变区基因片段(VH)能反映生殖分配、特应性皮炎儿童中的IgE转录子在几乎不表达VH2和 VH4家族中表现出显性。而在哮喘儿童中IgE转录子高度变异(7.2%),特应性皮炎中的体细胞突变率将少于高度变异的一半(3.4%)。此外,在特应性皮炎抗原选择诱导的转录子比例降低到11%(哮喘中为24%)。总之,IgE谱在儿童不同的过敏性疾病中有显著的变化。与哮喘儿童相比,患有特应性皮炎的学龄前儿童的IgE转录子明显突变较少,克隆不集中,抗原选择诱导较少。我们认为我们的数据与假设一致:在特应性皮炎中超抗原激活有助于IgE谱的突变和选择。
(杨冬 审校)
JImmunol.2016Jun15;196(12):4885-92.doi:10.4049/jimmunol.1402889.Epub2016May 9.
Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation.
Kerzel S1, Rogosch T2, Struecker B2, Maier RF2, Kabesch M3, Zemlin M2.
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Abstract
The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis.
JImmunol.2016Jun15;196(12):4885-92.doi:10.4049/jimmunol.1402889.Epub2016May 9.