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通过血清来源的细胞外囊泡蛋白质组学分析鉴定强直性脊柱炎的新型生物标志物。

Identifying novel biomarkers for ankylosing spondylitis through proteomic profiling of serum-derived extracellular vesicles.

作者信息

Sung Soo-Eun, Park Wook-Tae, Choi Joo-Hee, Kim Young-In, Ma Min-Jung, Son Wan-Suk, Park Sangbum, Lim Ju-Hyeon, Seo Min-Soo, Lee Gun Woo

机构信息

Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), 80 Chembok-ro, Dong-gu, Daegu, 41061, Republic of Korea.

Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Nam-gu, Daegu, 42415, Republic of Korea.

出版信息

Clin Exp Med. 2025 Jul 1;25(1):227. doi: 10.1007/s10238-025-01718-8.

DOI:10.1007/s10238-025-01718-8
PMID:40591022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12213980/
Abstract

The objective of this study is to analyze the protein composition of extracellular vesicles (EVs) isolated from the serum of ankylosing spondylitis (AS) patients to identify potential biomarkers that could enable the early diagnosis and intervention of this condition. Serum samples were collected from AS patients and controls. EVs were isolated from these samples using ExoQuick® ULTRA solution, and their morphology, size, and concentration were analyzed using transmission electron microscopy and nanoparticle tracking analysis. Proteins within the EVs were identified and quantified through liquid chromatography-mass spectrometry (LC-MS/MS), followed by validation of key proteins using enzyme-linked immunosorbent assay (ELISA). Data were analyzed to identify proteins significantly upregulated in AS patients compared with the levels in controls. Here, through LC-MS/MS analysis, we demonstrated that Fibulin-1 (FBLN1), von Willebrand factor (VWF), complement factor H-related protein 2 (CFHR2), and lysozyme C (LYZ) expression were significantly upregulated in serum-derived EVs from AS patients compared with the levels in controls. These findings were further validated by ELISA, confirming the potential utility of serum-derived EVs as specific biomarkers for AS. The elevated levels of FBLN1, VWF, CFHR2, and LYZ in the EVs of AS patients represent promising candidates for biomarkers in the early diagnosis and treatment of AS. Further research should be performed to validate these findings and explore their clinical applicability.

摘要

本研究的目的是分析从强直性脊柱炎（AS）患者血清中分离出的细胞外囊泡（EVs）的蛋白质组成，以确定能够实现该疾病早期诊断和干预的潜在生物标志物。从AS患者和对照组收集血清样本。使用ExoQuick® ULTRA溶液从这些样本中分离出EVs，并通过透射电子显微镜和纳米颗粒跟踪分析对其形态、大小和浓度进行分析。通过液相色谱-质谱联用（LC-MS/MS）对EVs中的蛋白质进行鉴定和定量，随后使用酶联免疫吸附测定（ELISA）对关键蛋白质进行验证。分析数据以确定与对照组水平相比在AS患者中显著上调的蛋白质。在此，通过LC-MS/MS分析，我们证明与对照组水平相比，AS患者血清来源的EVs中纤连蛋白-1（FBLN1）、血管性血友病因子（VWF）、补体因子H相关蛋白2（CFHR2）和溶菌酶C（LYZ）的表达显著上调。这些发现通过ELISA进一步得到验证，证实了血清来源的EVs作为AS特异性生物标志物的潜在用途。AS患者EVs中FBLN1、VWF、CFHR2和LYZ水平的升高代表了AS早期诊断和治疗中生物标志物的有前景的候选物。应进行进一步研究以验证这些发现并探索其临床适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/6ad4e20a7339/10238_2025_1718_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/78b93fa1aabe/10238_2025_1718_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/039c3352b153/10238_2025_1718_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/11e8dbb499e2/10238_2025_1718_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/e4dc857b5f84/10238_2025_1718_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/0655f27995a7/10238_2025_1718_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/6ad4e20a7339/10238_2025_1718_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/78b93fa1aabe/10238_2025_1718_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/039c3352b153/10238_2025_1718_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/11e8dbb499e2/10238_2025_1718_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/e4dc857b5f84/10238_2025_1718_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/0655f27995a7/10238_2025_1718_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4277/12213980/6ad4e20a7339/10238_2025_1718_Fig6_HTML.jpg

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本文引用的文献

[1]
A novel ultrasound-based score for assessing carotid artery activity in Takayasu's arteritis.

Clin Exp Rheumatol. 2025-4

[2]
Generation of induced pluripotent stem cells from an HLA-B27 positive ankylosing spondylitis patient with syndesmophyte formation.

Stem Cell Res. 2024-10

[3]
Serum metabolomics reveals the metabolic profile and potential biomarkers of ankylosing spondylitis.

Mol Omics. 2024-9-23

[4]
Association between Mycobacterium tuberculosis infection and the risk of inflammatory arthritides.

Clin Exp Rheumatol. 2024-9

[5]
Gut microbiome and metabolome to discover pathogenic bacteria and probiotics in ankylosing spondylitis.

Front Immunol. 2024

[6]
Extracellular vesicles as a new frontier of diagnostic biomarkers in osteosarcoma diseases: a bibliometric and visualized study.

Front Oncol. 2024-3-4

[7]
Diagnosis and Treatment of Ankylosing Spondylitis.

Cureus. 2024-1-19

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Inflammopharmacology. 2024-2

[9]
Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases.

J Nanobiotechnology. 2023-5-24

[10]
Optimized sample preparation and data analysis for TMT proteomic analysis of cerebrospinal fluid applied to the identification of Alzheimer's disease biomarkers.

Clin Proteomics. 2022-5-14

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