作为关节炎生物标记物的滑膜液细胞外囊泡:脂质分析和综合全息技术的附加值

L. Varela, Chris H.A. van de Lest, P. V. van Weeren, M. Wauben
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引用次数: 0

摘要

关节炎是一种多种多样的关节炎性疾病,给早期诊断和针对性治疗带来了巨大挑战。及时干预势在必行,但传统的诊断方法无法检测出细微的早期症状。因此,我们迫切需要能区分不同关节炎类型并进行早期诊断的特异性生物标志物。对这种精确诊断工具的追求促使人们对细胞外囊泡 (EV) 的兴趣与日俱增。细胞外囊泡由细胞以调节方式释放,可在体液中检测到,包括填充关节间隙的滑液(SF)。它们能让人了解关节炎错综复杂的分子结构,这也刺激了人们寻找基于 EV 的微创诊断方法。因此,分析 SF 中的 EVs 已成为确定基于 EV 的关节疾病内分型、预后和进展生物标志物的重点。EVs 由脂质双分子层和多种不同类型的货物组成,其中蛋白质和 RNA 已被广泛研究。相比之下,EVs 的膜脂质,尤其是特定脂质的丰度、存在或不存在及其对 EVs 生物活性的贡献,在 EVs 研究中大多被忽视。此外,鉴定EVs中协同作用的不同EV成分的特定组合有助于定义复合生物标志物。我们在此概述了有关 SF 衍生 EV 的最新知识,重点是脂质分析,并举例说明了蛋白质组学和脂质组学综合分析在寻找 EV 相关复合生物标记物方面的附加值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics
Arthritis, a diverse group of inflammatory joint disorders, poses great challenges in early diagnosis and targeted treatment. Timely intervention is imperative, yet conventional diagnostic methods are not able to detect subtle early symptoms. Hence, there is an urgent need for specific biomarkers that discriminate between different arthritis forms and for early diagnosis. The pursuit of such precise diagnostic tools has prompted a growing interest in extracellular vesicles (EVs). EVs, released by cells in a regulated fashion, are detectable in body fluids, including synovial fluid (SF), which fills the joint space. They provide insights into the intricate molecular landscapes of arthritis, and this has stimulated the search for minimally invasive EV-based diagnostics. As such, the analysis of EVs in SF has become a focus for identifying EV-based biomarkers for joint disease endotyping, prognosis, and progression. EVs are composed of a lipid bilayer and a wide variety of different cargo types, of which proteins and RNAs are widely investigated. In contrast, membrane lipids of EVs, especially the abundance, presence, or absence of specific lipids and their contribution to the biological activity of EVs, are largely overlooked in EV research. Furthermore, the identification of specific combinations of different EV components acting in concert in EVs can fuel the definition of composite biomarkers. We here provide a state-of-the-art overview of the knowledge on SF-derived EVs with emphasis on lipid analysis and we give an example of the added value of integrated proteomics and lipidomics analysis in the search for composite EV-associated biomarkers.
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