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α-半乳糖综合征中 Th2 偏向的 T 细胞与 B 细胞对 α-半乳糖和蜱抗原的反应相关。

Th2-skewed T cells correlate with B cell response to α-Gal and tick antigens in α-Gal syndrome.

机构信息

Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and University Hospital, Solna, Sweden.

Innovative Centre of the Faculty of Chemistry, Belgrade, Serbia.

出版信息

J Clin Invest. 2023 Mar 15;133(6):e158357. doi: 10.1172/JCI158357.

DOI:10.1172/JCI158357
PMID:36701195
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10014093/
Abstract

Tick bites have been shown to transmit a novel form of severe food allergy, the galactose-α-1,3-galactose (α-Gal) syndrome (AGS). Cellular responses to α-Gal in patients with AGS have, to date, not been thoroughly scrutinized. Therefore, we investigated T and B cell proliferation, activation, and cytokine profiles in response to tick protein extract (TE) and α-Gal-free TE in patients with AGS and in healthy controls. T and B cells from both patients and controls proliferated in response to TE, but significantly more in patients with AGS. B cell proliferation, but not T cell proliferation, in patients with AGS was reduced by removing α-Gal from the TE. In addition, TE induced a clear Th2 cytokine profile in patients with AGS. Expression of CD23 by B cells correlated only to T cell proliferation. However, both B cell proliferation and CD23 expression were reduced when CD40L and IL-4 were blocked. A large portion of the IgG1 and IgE antibodies binding TE in patients with AGS were directed against the α-Gal epitope. We have, for what we believe to be the first time, investigated T and B cell responses to α-Gal carrying tick proteins in patients with AGS, which will be essential for the understanding of the immune response against an allergenic carbohydrate transmitted by ticks.

摘要

蜱虫叮咬已被证明可传播一种新型严重食物过敏,即半乳糖-α-1,3-半乳糖(α-Gal)综合征(AGS)。迄今为止,尚未对 AGS 患者中针对 α-Gal 的细胞反应进行彻底研究。因此,我们研究了 AGS 患者和健康对照者对蜱蛋白提取物(TE)和不含 α-Gal 的 TE 的 T 和 B 细胞增殖、激活和细胞因子谱。来自患者和对照者的 T 和 B 细胞均对 TE 增殖,但 AGS 患者的增殖更为明显。从 TE 中去除 α-Gal 可减少 AGS 患者的 B 细胞增殖,但不会减少 T 细胞增殖。此外,TE 在 AGS 患者中诱导出明显的 Th2 细胞因子谱。B 细胞的 CD23 表达仅与 T 细胞增殖相关。但是,当阻断 CD40L 和 IL-4 时,B 细胞增殖和 CD23 表达均减少。在 AGS 患者中与 TE 结合的 IgG1 和 IgE 抗体的很大一部分针对 α-Gal 表位。我们首次研究了 AGS 患者中携带 α-Gal 的蜱蛋白的 T 和 B 细胞反应,这对于理解针对由蜱传播的过敏原性碳水化合物的免疫反应至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/c296cc0bb656/jci-133-158357-g035.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/880e6ede1914/jci-133-158357-g030.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/c523f9d3cd7f/jci-133-158357-g031.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/7e1976e814c6/jci-133-158357-g032.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/69cebdfd3503/jci-133-158357-g033.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/a77fc330447e/jci-133-158357-g034.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/c296cc0bb656/jci-133-158357-g035.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/880e6ede1914/jci-133-158357-g030.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/c523f9d3cd7f/jci-133-158357-g031.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/7e1976e814c6/jci-133-158357-g032.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/69cebdfd3503/jci-133-158357-g033.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/a77fc330447e/jci-133-158357-g034.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/101b/10014093/c296cc0bb656/jci-133-158357-g035.jpg

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本文引用的文献

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Trends Immunol. 2021 Jul;42(7):554-574. doi: 10.1016/j.it.2021.05.005. Epub 2021 May 30.
2
Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.蜱唾液腺提取物在缺乏α-半乳糖的小鼠中诱导α-半乳糖综合征。
Immun Inflamm Dis. 2021 Sep;9(3):984-990. doi: 10.1002/iid3.457. Epub 2021 May 25.
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Bovine γ-globulin, lactoferrin, and lactoperoxidase are relevant bovine milk allergens in patients with α-Gal syndrome.
连接α-半乳糖综合征的诊断与临床相关性——疑似α-半乳糖相关过敏患者的个体致敏模式
Nutrients. 2025 Apr 30;17(9):1541. doi: 10.3390/nu17091541.
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Pre-clinical strategies and emerging technologies driving advances in the alpha-gal syndrome.推动α-半乳糖综合征进展的临床前策略和新兴技术。
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