滑液
医学
生物标志物
病理
蛋白质组学
骨关节炎
粘多糖病
疾病
粘多糖病Ⅰ
软骨
生物标志物发现
病理生理学
滑膜
免疫学
炎症
酶替代疗法
生物
替代医学
解剖
基因
生物化学
作者
Chenghao Zhang,Rahul Gawri,Yian Khai Lau,Lynn A. Spruce,Hossein Fazelinia,Zhirui Jiang,Stephanie Y. Jo,Carla R. Scanzello,Wilfried Mai,George R. Dodge,Margret L. Casal,Lachlan J. Smith
标识
DOI:10.1016/j.ymgme.2023.107371
摘要
Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I. Synovial fluid and serum samples were collected from MPS I and healthy dogs at 12 months-of-age, and protein abundance characterized using liquid chromatography tandem mass spectrometry. Stifle joints were evaluated postmortem using magnetic resonance imaging (MRI) and histology. Proteomics identified 40 proteins for which abundance was significantly correlated between serum and synovial fluid, including markers of inflammatory joint disease and lysosomal dysfunction. Elevated expression of three biomarker candidates, matrix metalloproteinase 19, inter-alpha-trypsin inhibitor heavy-chain 3 and alpha-1-microglobulin, was confirmed in MPS I cartilage, and serum abundance of these molecules was found to correlate with MRI and histological degenerative grades. The candidate biomarkers identified have the potential to improve patient care by facilitating minimally-invasive, specific assessment of joint disease progression and response to therapeutic intervention.
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