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首页> 外文期刊>Infection and immunity >Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2.
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Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2.

机译:对人淋巴丝虫病中特定抗原的差异抗体同种型反应性:gp15 / 400优先诱导免疫球蛋白E(IgE),IgG4和IgG2。

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Lymphatic filarial infection in humans is associated with a strong skewing of the immune response towards the TH2 arm, with prominent interleukin 4-producing cells and elevated levels of immunoglobulin G4 (IgG4) and IgE antibodies in peripheral blood. To determine how such a generalized TH2 imbalance governs responses to individual parasite antigens, the profiles of isotypes of antibodies to two recombinant proteins of Brugia spp. were studied. One molecule was the C-terminal portion of the filarial heat shock protein 70 (Bpa-26), representative of a cytoplasmic protein, and the second antigen was a single unit of the tandem repeats of a Brugia polypeptide (BpL-4), a secreted product which is prominently exposed to the immune system. Serum samples from 146 individuals resident in areas in which brugian filariasis is endemic were used, and it was found that whereas the levels of IgG1 and IgG3 responses to both Bpa-26 and BpL-4 were high, IgG4 and IgE antibodies to only BpL-4, not to Bpa-26, were prominent. Thus, an antigen which is chronically exposed to the immune system elicited a TH2-dependent isotype switch, as manifested by increased IgG4 and IgE responses. Moreover, IgG4 and IgE responses to BpL-4 showed a strong negative association, suggesting that mediators other than interleukin 4 must be responsible for such differential regulation of these two isotypes. When the data were analyzed as a function of clinical status, a striking association between elevated levels of IgG3 antibodies to Bpa-26 and manifestation of chronic obstructive disease was found; elephantiasis patients showed significantly higher levels of IgG3 antibodies to Bpa-26 than microfilaremics and asymptomatic amicrofilaremics. This indicates that an imbalance of isotypes of antibodies to particular filarial antigens might play a role in the pathogenesis of chronic disease.
机译:人的淋巴丝虫感染与针对TH2臂的免疫反应的强烈偏斜相关,与突出产生白介素4的细胞以及外周血中免疫球蛋白G4(IgG4)和IgE抗体水平升高有关。为了确定这种普遍的TH2不平衡如何控制对单个寄生虫抗原的反应,需要针对两种布鲁氏菌属重组蛋白的抗体同种型。被研究了。一个分子是丝状热休克蛋白70(Bpa-26)的C端部分,代表细胞质蛋白,第二个抗原是Brugia多肽(BpL-4)串联重复序列的单个单元,显着暴露于免疫系统的分泌产物。使用了来自比利时丝虫病流行地区的146个人的血清样本,发现对Bpa-26和BpL-4的IgG1和IgG3的反应水平很高,而对BpL- 4,不以Bpa-26为名。因此,长期暴露于免疫系统的抗原引起TH2依赖性同种型转换,如增加的IgG4和IgE反应所显示。此外,对BpL-4的IgG4和IgE反应显示出强烈的负相关性,表明白介素4以外的其他介体必须负责这两种同种型的这种差异调节。当根据临床状况对数据进行分析时,发现针对Bpa-26的IgG3抗体水平升高与慢性阻塞性疾病的表现之间存在惊人的联系。象皮病患者显示的针对Bpa-26的IgG3抗体水平明显高于微丝线虫和无症状的微丝线虫。这表明针对特定丝状抗原的抗体同种型的失衡可能在慢性疾病的发病机理中起作用。

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