The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias
The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias
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DOI：
10.1016/j.jaci.2007.05.035
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发表时间：
2007-09-01
影响因子：
14.2
通讯作者：
Mempel, Martin
中科院分区：
文献类型：
--
作者：
Lim, Annick;Luderschmidt, Stephan;Mempel, Martin
背景：特应性疾病患者的特征是高水平的特异性IgE产生。然而，鲜为人知的是，他们的B细胞repertoires.Objectives的组成：我们试图分析完整的PBMC来源的IgE库，并比较不同patients.Methods之间的克隆expansions：我们分析了IgE轴承的B细胞受体库高度特应性患者（> 1000 IU/mL）使用定量RT-PCR，互补决定区3光谱，和序列分析。三个代表性的患者，另外在抗IgE therapy.Results：特应性患者表现出100至1000倍的IgE特异性转录比对照个体。这些患者使用与其IgM和IgG库高度相似的重免疫球蛋白链（VH）E库的可变区，优选VH 3b、VH 4、VH 3a和VH 1区段。每个患者都有单独的克隆扩增，最有可能是过敏原特异性IgE产生的相关性。在光谱分析中发现了几个具有相似致敏模式的个体所共有的互补决定区3内的共同扩增。然而，这些抗原驱动的扩增在序列水平上显示出差异。在奥马珠单抗治疗的患者的临床改善是由一个明显的增加IgG/IgE的transcriptions.Conclusion：过敏性患者的IgE库如下的VH使用模式，看到其他免疫球蛋白，似乎优先招募个人重排，而不是公共的扩张。临床含义：对IgE B细胞库的详细分析非常适合于跟踪不同治疗方式期间IgE使用的变化。
Background: Patients with atopic diseases are characterized by high levels of specific IgE production. However, little is known about the composition of their B-cell repertoires.Objectives: We sought to analyze the complete PBMC-derived IgE repertoire and to compare clonal expansions between different patients.Methods: We have analyzed the IgE-bearing B-cell receptor repertoire in highly atopic patients (> 1000 IU/mL) using quantitative RT-PCR, complementarity determining region 3 spectratyping, and sequence analysis. Three representative patients were additionally followed during anti-IgE therapy.Results: Atopic patients exhibited 100 to 1000 times more IgE-specific transcripts than control individuals. These patients used a variable region of the heavy immunoglobulin chain (VH) E repertoire highly similar to their IgM and IgG repertoires, with preference of VH3b, VH4, VH3a, and VH1 segments. Each patient harbored individual clonal expansions, most probably as correlation of allergen-specific IgE production. Common expansions within the complementary determining region 3 shared by several individuals with similar sensitization patterns were found in spectratyping analysis. However, these antigen-driven expansions showed differences on the sequence level. In omalizumab-treated patients the clinical improvement was paralleled by a clear increase in the ratio of IgG/IgE transcripts.Conclusion: The IgE repertoire in atopic patients follows the VH use patterns seen for other immunoglobulins and seems to preferentially recruit individual rearrangements rather than public expansions. Clinical implications: The detailed analysis of the IgE B-cell repertoire is highly suitable to follow changes in IgE uses during different therapy modalities.