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模拟麻风分枝杆菌和宿主之间的 B 和 T 细胞表位作为麻风 1 型反应的预测生物标志物。

Mimicking B and T cell epitopes between Mycobacterium leprae and host as predictive biomarkers in type 1 reaction in leprosy.

机构信息

Stanley Browne Laboratory, The Leprosy Mission Community Hospital, Nand Nagari, Shahdara, New Delhi, India, 110093.

GLA University, Mathura, UP, India, 281406.

出版信息

Sci Rep. 2021 Dec 24;11(1):24431. doi: 10.1038/s41598-021-04135-5.

DOI:10.1038/s41598-021-04135-5
PMID:34952925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8709860/
Abstract

Several Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host. Presence of autoantibodies like, rheumatoid factor, anti-nuclear factor and antibodies to host, collagen, keratin, myelin basic protein (MBP) and myosin, have been earlier reported in leprosy patients. In the present study, we detected the role of mimicking epitopes between Mycobacterium leprae and host components in the induction of autoimmune response in leprosy. Based on our previous findings, we predicted and synthesized a total of 15 mimicking linear B cell epitopes (BCE) and 9 mimicking linear T cell epitopes (TCE) of keratin and MBP. Humoral and cell-mediated immune responses against these epitopes were investigated in Non-reaction (NR), Type 1 reaction (T1R) leprosy patients, and healthy controls. We observed significantly higher levels of antibodies against 8 BCE in T1R in comparison to NR leprosy patients. Further, we also found 5 TCE significantly associated with lymphocyte proliferation in the T1R group. Our results indicated that these epitopes play a key role in the induction of autoimmune response in leprosy and are also strongly associated with the inflammatory episodes of T1R. Conclusively, these molecules may be employed as a biomarker to predict the inflammatory episodes of T1R.

摘要

几种分枝杆菌感染,包括麻风病和结核病,已知通过调节宿主的内稳机制来引发自身免疫反应。以前曾在麻风病患者中报道过类风湿因子、抗核因子和针对宿主胶原、角蛋白、髓鞘碱性蛋白 (MBP) 和肌球蛋白的抗体等自身抗体的存在。在本研究中,我们检测了麻风分枝杆菌和宿主成分之间模拟表位在麻风病自身免疫反应诱导中的作用。基于我们之前的发现,我们预测并合成了总共 15 个模拟线性 B 细胞表位 (BCE) 和 9 个模拟线性 T 细胞表位 (TCE) 的角蛋白和 MBP。在非反应 (NR)、1 型反应 (T1R) 麻风病患者和健康对照者中,我们研究了针对这些表位的体液和细胞介导免疫反应。与 NR 麻风病患者相比,我们观察到 T1R 中针对 8 个 BCE 的抗体水平显著升高。此外,我们还发现 5 个 TCE 与 T1R 组淋巴细胞增殖显著相关。我们的结果表明,这些表位在麻风病自身免疫反应的诱导中起关键作用,并且与 T1R 的炎症发作也密切相关。总之,这些分子可以作为预测 T1R 炎症发作的生物标志物。

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Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.麻风分枝杆菌蛋白(50S 核糖体蛋白 L2 和赖氨酸 tRNA 合成酶)与髓鞘碱性蛋白之间的分子模拟:麻风病中神经损伤的可能机制。
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