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关节炎中的外泌体蛋白质生物标志物:解读类风湿性关节炎和骨关节炎的炎症特征

Exosomal Protein Biomarkers in Arthritis: Deciphering the Inflammatory Profiles of RA and OA.

作者信息

Brenis Gómez Claudia M, Plasencia-Rodríguez Chamaida, Novella-Navarro Marta, Martínez-Feito Ana, Balsa Alejandro, Calvo-Aranda Enrique, Hernández-Breijo Borja

机构信息

Immuno-Rheumatology Research Group, La Paz Hospital Institute for Health Research (IdiPAZ), 28046 Madrid, Spain.

VIB-UGent Inflammation Research Center, 9052 Gent, Belgium.

出版信息

Biomedicines. 2025 May 23;13(6):1283. doi: 10.3390/biomedicines13061283.

Abstract

: Rheumatoid arthritis (RA) and osteoarthritis (OA) are highly prevalent diseases and their pathophysiology, diagnosis and treatment continue to be challenging. The aim of this study was to characterize and differentiate the profiles of the serum extracellular vesicles (EVs) isolated from RA and OA patients. : This study included nine patients diagnosed with RA, eight patients with OA during a flare and five healthy controls (HCs). Blood samples were collected and EVs from the serum were isolated for further performance of flow cytometry and proteomic analysis. : The extracellular vesicles from HC samples exhibited smaller sizes and were more concentrated than exosomes from RA and OA samples. Surface protein expression was analyzed by flow cytometry. The results showed an enrichment of exosomes derived from antigen-presenting cells in RA samples; this was evidenced by their expression of CD14 and HLA-DR. Proteomic analysis identified 45 differentially expressed proteins between RA and OA patients. Furthermore, Ingenuity Pathway Analysis (IPA) identified inflammatory pathways such as the IL-1β and IL-6 signaling pathways as being enhanced in RA-derived exosomes, while the MYC and ROCK2 signaling pathways were enhanced in OA-derived exosomes. : Our results show serum-derived exosomes from RA and OA patients harbor different surface proteins and cargo profiles, mirroring the different pathophysiologic mechanisms underlying these diseases. These results also highlight the promising use of exosomes as disease biomarkers.

摘要

类风湿性关节炎(RA)和骨关节炎(OA)是高度流行的疾病,其病理生理学、诊断和治疗仍然具有挑战性。本研究的目的是对从RA和OA患者中分离出的血清细胞外囊泡(EVs)的特征进行描述并加以区分。

本研究纳入了9例确诊为RA的患者、8例处于病情发作期的OA患者以及5名健康对照者(HCs)。采集血样并从血清中分离出EVs,以进一步进行流式细胞术和蛋白质组学分析。

来自HC样本的细胞外囊泡尺寸较小且比来自RA和OA样本的外泌体更浓缩。通过流式细胞术分析表面蛋白表达。结果显示RA样本中源自抗原呈递细胞的外泌体富集;这通过它们对CD14和HLA - DR的表达得到证实。蛋白质组学分析确定了RA和OA患者之间45种差异表达的蛋白质。此外, Ingenuity通路分析(IPA)确定炎症通路如IL - 1β和IL - 6信号通路在源自RA的外泌体中增强,而MYC和ROCK2信号通路在源自OA的外泌体中增强。

我们的结果表明,来自RA和OA患者的血清来源外泌体具有不同的表面蛋白和货物谱,反映了这些疾病潜在的不同病理生理机制。这些结果还突出了外泌体作为疾病生物标志物的潜在应用前景。

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