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结核病中的自身免疫性疾病与分子模拟

Autoimmune Diseases and Molecular Mimicry in Tuberculosis.

作者信息

Churilov Leonid P, Normatov Muslimbek G, Ling Hong, Zhuang Min, Kudlay Dmitry, Starshinova Anna

机构信息

Department of Pathology and Laboratory of the Microangiopathic Mechanisms of Atherogenesis, Saint Petersburg State University, St. Petersburg 199034, Russia.

Department of Microbiology and Immunology, Harbin Medical University, Harbin 150088, China.

出版信息

Biology (Basel). 2024 Dec 22;13(12):1083. doi: 10.3390/biology13121083.

Abstract

UNLABELLED

Comorbidities in tuberculosis patients are increasing annually. Autoimmune pathology may influence the diagnosis and treatment of tuberculosis (TB). However, the molecular mimicry between (Mtb) and human autoantigens is an important provocative factor in the development of autoimmunity on one hand. Mtb has already been widely discussed as a provocateur of autoimmunity in humans. The aim of this study was to determine whether molecular mimicry exists between Mtb antigens and human autoantigens previously demonstrated as targets of autoimmunity.

MATERIALS AND METHODS

We analyzed the level of antibodies in 19 patients with pulmonary tuberculosis. In all cases ELISA assays was used. Also, in parallel, we identified 29 similar pentapeptides between key Mtb antigens and human autoantigens. Bioinformatic methods were used in this study. All amino acid sequences of MT antigens and human autoantigens were obtained from the UniProt database, and similar epitopes between Mtb antigens and human autoantigens were identified using the original "Alignmentaj" program. The immunoreactivity of the shared pentapeptides in Mtb antigens was evaluated with use of the IEDB database.

RESULTS

The high level of antibodies to modified citrulinated vimentin (anti-MCV) was most frequently detected (57%) in comparison with other antibodies. Elevated levels of antibodies to C3 complement fragments (47%) and rheumatoid factors (21%) in the absence of any rheumatic or autoimmune diseases are noteworthy. Several of the shared pentapeptides belong to the immunoreactive epitopes of Mtb antigens. The bioinformatic data correlated with our earlier studies of the levels of corresponding autoantibodies in the sera of TB patients.

CONCLUSION

Our findings on cross-reactivity and sequence similarity between the Mtb proteins and human autoantigens provide support for the role of antigen mimicry in TB-related autoimmunity.

摘要

未标注

结核病患者的合并症每年都在增加。自身免疫性病理可能会影响结核病(TB)的诊断和治疗。然而,结核分枝杆菌(Mtb)与人类自身抗原之间的分子模拟一方面是自身免疫发展的重要诱发因素。Mtb作为人类自身免疫的诱发因素已经得到了广泛讨论。本研究的目的是确定Mtb抗原与先前被证明为自身免疫靶点的人类自身抗原之间是否存在分子模拟。

材料与方法

我们分析了19例肺结核患者的抗体水平。所有病例均采用酶联免疫吸附测定(ELISA)。同时,我们还在关键的Mtb抗原和人类自身抗原之间鉴定出29个相似的五肽。本研究使用了生物信息学方法。MT抗原和人类自身抗原的所有氨基酸序列均从UniProt数据库获得,并使用原始的“Alignmentaj”程序鉴定Mtb抗原和人类自身抗原之间的相似表位。利用免疫表位数据库(IEDB)评估Mtb抗原中共享五肽的免疫反应性。

结果

与其他抗体相比,最常检测到高水平的抗瓜氨酸化波形蛋白抗体(抗MCV)(57%)。在没有任何风湿性或自身免疫性疾病的情况下,C3补体片段抗体水平升高(47%)和类风湿因子水平升高(21%)值得关注。一些共享的五肽属于Mtb抗原的免疫反应性表位。生物信息学数据与我们早期对结核病患者血清中相应自身抗体水平的研究相关。

结论

我们关于Mtb蛋白与人类自身抗原之间交叉反应性和序列相似性的研究结果为抗原模拟在结核病相关自身免疫中的作用提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b946/11673594/cf684e5a220c/biology-13-01083-g001.jpg

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