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双歧杆菌和乳杆菌各组分在自身免疫性甲状腺疾病发病机制及血清学诊断中的作用。

The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases.

机构信息

Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Republic of Belarus.

出版信息

Benef Microbes. 2011 Jun;2(2):139-54. doi: 10.3920/BM2010.0011.

Abstract

During recent years, researchers have been focusing on the concept of an infectious etiology of autoimmune diseases. The most discussed theory is molecular mimicry, i.e. the emergence of autoreactive clones of T- and B-lymphocytes as a result of cross-immune response to homologous bacterial or viral antigen. Information on the role of probiotic microorganisms (PM) in the molecular mechanisms of autoimmune thyroid diseases (ATD) is limited. Using proteins and immunogenic peptides databanks and relevant computer programs, the homology between the amino acid sequences of thyroid peroxidase (TPO) and thyroglobulin (Tg), which are potential B- and T-cell epitopes of these antigens, and proteins of bifidobacteria and lactobacilli was established. Moreover, we have found components of cells of Bifidobacterium bifidum 791, Bifidobacterium adolescentis 94 BIM, Bifidobacterium longum B379M and Lactobacillus plantarum B-01 that selectively bind human antibodies to TPO (anti-TPO) and antibodies to Tg (anti-Tg) and compete with natural antigens for the binding of anti-TPO and anti-Tg in ELISA. Additionally, a three-fold difference was observed between the probability of detecting antibodies (Abs) to the antigens of L. plantarum B-01 and B. bifidum 791 in serum samples containing and those not containing anti-TPO. On the whole, our data are arguments in favour of the assumption of the possible role of PM of the genera Bifidobacterium and Lactobacillus in triggering ATD by the mechanism of molecular mimicry. The data obtained in silico and in vitro should be proven by use of animal models and clinical studies for extrapolations to the whole body. Possible antigenic properties of components/proteins of bifidobacteria and lactobacilli, selectively binding anti-TPO and anti-Tg should be taken into consideration. Natural human Abs to these bacterial components are probably able to cross-react with the TPO and Tg in the ELISA for detection of anti-TPO and anti-Tg, which are serologic markers of ATD. It can lead to unspecific false positive results and, hence, to an incorrect diagnosis.

摘要

近年来,研究人员一直专注于自身免疫性疾病的传染性病因概念。讨论最多的理论是分子模拟,即 T 和 B 淋巴细胞的自身反应性克隆的出现是由于对同源细菌或病毒抗原的交叉免疫反应。关于益生菌微生物(PM)在自身免疫性甲状腺疾病(ATD)的分子机制中的作用的信息是有限的。使用蛋白质和免疫原性肽数据库和相关的计算机程序,建立了甲状腺过氧化物酶(TPO)和甲状腺球蛋白(Tg)的氨基酸序列之间的同源性,这些抗原是这些抗原的潜在 B 和 T 细胞表位,以及双歧杆菌和乳杆菌的蛋白质之间的同源性。此外,我们发现双歧杆菌 791、双歧杆菌少年 94 BIM、长双歧杆菌 B379M 和植物乳杆菌 B-01 的细胞成分选择性结合人抗 TPO(抗 TPO)和抗 Tg(抗 Tg)抗体,并在 ELISA 中与天然抗原竞争抗 TPO 和抗 Tg 的结合。此外,在含有和不含有抗 TPO 的血清样本中,检测到对 L. plantarum B-01 和 B. bifidum 791 抗原的抗体(Abs)的可能性之间存在三倍差异。总的来说,我们的数据支持了 PM 的可能作用的假设,即双歧杆菌属和乳杆菌属的 PM 通过分子模拟机制触发 ATD。体内和体外获得的数据应通过使用动物模型和临床研究来证明,以便外推到整个机体。应考虑双歧杆菌和乳杆菌的成分/蛋白质的可能抗原性,这些成分/蛋白质选择性地结合抗 TPO 和抗 Tg。这些细菌成分的天然人 Abs 可能能够与 TPO 和 Tg 在用于检测抗 TPO 和抗 Tg 的 ELISA 中发生交叉反应,抗 TPO 和抗 Tg 是 ATD 的血清学标志物。这可能导致非特异性假阳性结果,从而导致错误诊断。

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