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使用噬菌体展示系统筛选糖尿病相关自身抗原和血清抗体谱

Screening of Diabetes-Associated Autoantigens and Serum Antibody Profiles Using a Phage Display System.

作者信息

Lin Jun, Wang Zhenyu, Wang Hongtao, Li Yuping, Liu Yao, He Yige, Liu Qian, Chen Zichuan, Ji Yuan

机构信息

Shenzhen Institute for Drug Control (Shenzhen Testing Center of Medical Devices), No. 28, Gaoxin Central 2nd Avenue, Nanshan, Shenzhen 518057, China.

Shenzhen Blot Bio-Products Ltd, Nanshan Knowledge Service Building, 3025 Nanhai Avenue, Nanshan, Shenzhen 518052, China.

出版信息

Int J Microbiol. 2024 Oct 24;2024:1220644. doi: 10.1155/2024/1220644. eCollection 2024.

DOI:10.1155/2024/1220644
PMID:39483642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11527542/
Abstract

Phage display method is a crucial tool to find novel clinically valuable diabetes-associated autoantigens and identify known autoantigen epitopes that are associated with diabetes and could provide scientific support and guidance for the artificial construction and synthesis of Type I diabetes mellitus (T1DM) novel biomarkers. The phage display system was used for the "biopanning" of T1DM serum. Following the sequencing of the phage DNAs, the homologous sequences of the above fusion heptapeptide were further investigated by BLAST to track the origin of the polypeptide sequences. The antibody spectrum revealed new T1DM-associated epitopes and antibodies. A total of 1200 phage DNA were sequenced and 9 conserved polypeptide sequences were collected. It was confirmed that the zinc transporter and islet amyloid protease were among them. The conserved polypeptide sequence 8 and another three distinctive polypeptide sequences derived from Proteus were discovered. Furthermore, we expressed recombinant proteins with homologous polypeptide sequences for the human islet amyloid polypeptide (IAPP) and polypeptide precursor human zinc transporter 8 (ZNT8). Through clinical sample detection for the serum from T1DM ( = 100) and T2DM ( = 200) patients, results demonstrate the importance and relevance of these polypeptides in the recognition and classification of various forms of diabetes. Human pancreatic and concurrent bacterial-derived protein antigens and their epitopes were identified in this research by the phage display system, which is crucial for distinguishing different types of diabetes.

摘要

噬菌体展示方法是寻找新型具有临床价值的糖尿病相关自身抗原以及鉴定与糖尿病相关的已知自身抗原表位的关键工具,可为I型糖尿病(T1DM)新型生物标志物的人工构建和合成提供科学支持与指导。噬菌体展示系统用于对T1DM血清进行“淘选”。在对噬菌体DNA进行测序后,通过BLAST进一步研究上述融合七肽的同源序列,以追踪多肽序列的来源。抗体谱揭示了新的T1DM相关表位和抗体。共对1200个噬菌体DNA进行了测序,收集到9个保守多肽序列。证实其中包括锌转运体和胰岛淀粉样蛋白酶。发现了保守多肽序列8以及另外三个源自变形杆菌的独特多肽序列。此外,我们表达了与人胰岛淀粉样多肽(IAPP)和人锌转运体8(ZNT8)多肽前体具有同源多肽序列的重组蛋白。通过对100例T1DM患者和200例T2DM患者的血清进行临床样本检测,结果证明了这些多肽在各种形式糖尿病的识别和分类中的重要性和相关性。本研究通过噬菌体展示系统鉴定了人胰腺及同时存在的细菌来源的蛋白抗原及其表位,这对于区分不同类型的糖尿病至关重要。

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本文引用的文献

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Applications of the phage display technology in molecular biology, biotechnology and medicine.噬菌体展示技术在分子生物学、生物技术和医学中的应用。
Crit Rev Microbiol. 2024 Aug;50(4):450-490. doi: 10.1080/1040841X.2023.2219741. Epub 2023 Jun 4.
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Type 1 Diabetes Mellitus.1型糖尿病
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Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer's disease.胰岛淀粉样多肽交叉成核tau 并驱动阿尔茨海默病中的神经纤维病理。
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Identification of Serum Biomarkers for Systemic Lupus Erythematosus Using a Library of Phage Displayed Random Peptides and Deep Sequencing.基于噬菌体展示随机肽文库和深度测序技术鉴定系统性红斑狼疮的血清生物标志物。
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Deficiency of ZnT8 Promotes Adiposity and Metabolic Dysfunction by Increasing Peripheral Serotonin Production.ZnT8 缺乏通过增加外周 5-羟色胺的产生促进肥胖和代谢功能障碍。
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