Sabol Jenny K, Wei Wei, López-Hoyos Marcos, Seo Youjin, Andaya Armann, Leary Julie A
Department of Molecular & Cellular Biology, University of California, Davis, California 95616, USA.
Department of Chemistry, University of California, Davis, California 95616, USA.
Matrix Biol. 2014 Nov;40:54-61. doi: 10.1016/j.matbio.2014.08.016. Epub 2014 Sep 11.
Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC-MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future.
硫酸乙酰肝素（HS）是一种复杂且高度可变的多糖，作为HS蛋白聚糖（HSPG）普遍表达于细胞表面，并以游离HS片段的形式存在于细胞外基质中。其因各种乙酰化和硫酸化模式而具有的异质性赋予了多种功能。在动物组织中，HS与多种蛋白质相互作用以介导众多生物活性；鉴于其在炎症过程中的多种作用，对人血清中HS的表征对于阐明疾病机制具有重要潜力。历史上，HS的研究受到其在人血清中低浓度以及血清基质复杂性的限制。在本研究中，我们使用改良的质谱方法检测了50名类风湿性关节炎（RA）女性患者血清中的HS二糖谱，并将我们的结果与51名健康女性的血清进行了比较。通过使用各种纯化方法和在线LC-MS/MS，我们发现不同人群之间在硫酸化和乙酰化模式上存在统计学上的显著差异。由于RA的早期诊断被认为对减缓疾病进展很重要，识别特定的生物分子特征可能为开发新的早期抑制该疾病的疗法提供关键信息。这是在人血清中发现的RA潜在糖胺聚糖生物标志物的首次报告，同时也承认未来需要研究更大的人群样本和更严格的收集参数这一明显事实。
