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对. 丝氨酸蛋白酶样蛋白的过敏反应

Allergic Reactions to Serine Protease-Like Proteins of .

机构信息

Department of Immunology, Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.

Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.

出版信息

Front Immunol. 2021 Mar 23;12:651060. doi: 10.3389/fimmu.2021.651060. eCollection 2021.

Abstract

In cystic fibrosis (CF) infectious and allergic airway inflammation cause pulmonary exacerbations that destroy the lungs. is a common long-term colonizer and cause of recurrent airway infections in CF. The pathogen is also associated with respiratory allergy; especially the staphylococcal serine protease-like proteins (Spls) can induce type 2 immune responses in humans and mice. We measured the serum IgE levels specific to 7 proteases of by ELISA, targeting 5 Spls (76 CF patients and 46 controls) and the staphopains A and B (16 CF patients and 46 controls). Then we compared cytokine release and phenotype of T cells that had been stimulated with Spls between 5 CF patients and 5 controls. CF patients had strongly increased serum IgE binding to all Spls but not to the staphopains. Compared to healthy controls, their Spl-stimulated T cells released more type 2 cytokines (IL-4, IL-5, IL-13) and more IL-6 with no difference in the secretion of type 1- or type 3 cytokines (IFNγ, IL-17A, IL-17F). IL-10 production was low in CF T cells. The phenotype of the Spl-exposed T cells shifted towards a Th2 or Th17 profile in CF but to a Th1 profile in controls. Sensitization to Spls is common in CF. This discovery could explain episodes of allergic inflammation of hitherto unknown causation in CF and extend the diagnostic and therapeutic portfolio.

摘要

在囊性纤维化 (CF) 中,传染性和过敏性气道炎症导致肺部恶化。金黄色葡萄球菌是 CF 患者中常见的长期定植菌和反复呼吸道感染的原因。该病原体也与呼吸道过敏有关;特别是葡萄球菌丝氨酸蛋白酶样蛋白 (Spl) 可以在人类和小鼠中诱导 2 型免疫反应。我们通过 ELISA 测量了 7 种蛋白酶的血清特异性 IgE 水平,针对 5 种 Spl(76 例 CF 患者和 46 例对照)和葡萄球菌蛋白酶 A 和 B(16 例 CF 患者和 46 例对照)。然后,我们比较了 5 例 CF 患者和 5 例对照的 Spl 刺激后的 T 细胞的细胞因子释放和表型。CF 患者的血清 IgE 与所有 Spl 结合显著增加,但与葡萄球菌蛋白酶不结合。与健康对照组相比,他们的 Spl 刺激的 T 细胞释放更多的 2 型细胞因子(IL-4、IL-5、IL-13)和更多的 IL-6,而 1 型或 3 型细胞因子(IFNγ、IL-17A、IL-17F)的分泌没有差异。CF T 细胞的 IL-10 产生量较低。暴露于 Spl 的 T 细胞在 CF 中向 Th2 或 Th17 表型转移,但在对照中向 Th1 表型转移。对 Spls 的过敏在 CF 中很常见。这一发现可以解释 CF 中迄今未知病因的过敏炎症发作,并扩展诊断和治疗组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b6/8021911/5ada19977e90/fimmu-12-651060-g001.jpg

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