Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis.
Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis.
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DOI：
10.1016/j.jaci.2010.11.007
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Nutman TB
中科院分区：
文献类型：
--
作者：
Santiago HC;Bennuru S;Boyd A;Eberhard M;Nutman TB
“卫生假说”认为，寄生虫感染可调节宿主免疫反应，减少特应性。其他数据表明，寄生虫感染可能会引发过敏反应。评估已知的屋尘病原肌球蛋白过敏原和丝虫性原肌球蛋白之间的结构和免疫学关系。比较了OvTrop和Delp10在分子、结构和免疫学上的关系。比较了感染丝虫和未感染屋尘螨特应性个体血清中OvTrop和Der p10特异性IgE、Ig G和Ig G4的水平，以及感染丝虫寄生虫Loa Loa的非人灵长类动物的反应。交叉反应性通过抗原介导的耗竭试验进行比较，功能通过被动嗜碱性细胞致敏进行比较。丝虫原肌球蛋白和螨原肌球蛋白非常相似，在氨基酸水平上有72%的同源性，并且预测的3D结构重叠。丝虫感染者与非感染者相比，Der p10的IgE和Ig G抗体阳性率明显升高。血清Ov-和Der-p10-原肌球蛋白特异性Ig E、Ig G和Ig G4水平之间有很强的相关性(P<；0.0001；r>；0.79)。预先将抗Der p 10阳性受试者的血清与OvTrop完全耗尽的IgE、Ig G和抗Der p 10的IgG4抗体孵育。用对Der p 10过敏的人的血清致敏的嗜碱性粒细胞在被Ovtrop或Der p 10触发时释放类似的组胺。实验感染L.Loa的灵长类动物产生与Der p 10交叉反应的IgE。丝虫感染诱导强烈的交叉反应抗原肌球蛋白抗体反应，这可能影响过敏反应的敏化和调节。
The "Hygiene Hypothesis" suggests that parasitic infection modulates host immune responses and decreases atopy. Other data suggest parasitic infections may induce allergic responsiveness. Assess the structural and immunologic relationships between the known Dermatophagoides pteronyssinus (Der p 10) tropomyosin allergen and filarial tropomyosin (OvTrop). The molecular, structural, and immunologic relationships between OvTrop and Der p 10 were compared. Levels of OvTrop- and Der p 10-specific IgE, IgG, and IgG4 in sera of filaria-infected and –uninfected D. pteronyssinus-atopic individuals were compared as were the responses in nonhuman primates infected with the filarial parasite Loa loa. Crossreactivity was compared by antigen-mediated depletion assays and functionality by passive basophil sensitization. Filarial and mite tropomyosins were very similar, with 72% identity at the amino acid level and overlapping predicted 3D structures. The prevalence of IgE and IgG to Der p 10 was increased in filaria-infected individuals compared with uninfected subjects. There was a strong correlation between serum levels of Ov- and Der p 10-tropomyosin-specific IgE, IgG, and IgG4 (P < 0.0001; r > 0.79). Pre-incubation of sera from anti-Der p 10 positive subjects with OvTrop completely depleted IgE, IgG, and IgG4 anti-Der p 10. Basophils sensitized with sera from individuals allergic to Der p 10 released histamine similarly when triggered with OvTrop or Der p 10. Primates experimentally infected with L. loa developed IgE that crossreacted with Der p 10. Filarial infection induces strong crossreactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.
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