Genos Glycoscience Research Laboratory, Zagreb, Croatia.
Genos Glycoscience Research Laboratory, Zagreb, Croatia; St. Catherine Specialty Hospital, Zabok/Zagreb, Croatia.
Biochim Biophys Acta Gen Subj. 2018 Oct;1862(10):2124-2133. doi: 10.1016/j.bbagen.2018.07.003. Epub 2018 Jul 5.
Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.
Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery.
We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP.
Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation.
To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.
腰痛（LBP）是一组综合征的症状，这些综合征的潜在机制和分子病理学具有异质性，这使得治疗选择和患者预后极具挑战性。此外，LBP 的症状和预后受年龄、性别、职业、习惯和心理因素的影响。LBP 可能以潜在的炎症过程为特征。先前的研究表明，炎症反应与总血浆 N-糖基化之间存在联系。我们希望确定与慢性下腰痛（CLBP）相关的总血浆 N-糖基化模式的潜在变化，这可以深入了解疾病的发病机制。
在意大利、比利时和克罗地亚的临床中心收集了 1128 例 CLBP 患者和 760 例健康对照者的血浆样本，并在 N-糖链释放、荧光标记和净化后，使用亲水作用超高效液相色谱（HILIC-UPLC）进行 N-糖基化谱分析。观察到的 N-糖基化谱与接受腹部手术的 126 例急性炎症患者的队列进行了比较。
我们发现与健康对照组相比，CLBP 患者血浆糖蛋白上高分支（三触角和四触角）N-聚糖结构的相对含量有统计学意义的增加。此外，二唾液酸化和三唾液酸化糖链结构的相对含量增加，而 CLBP 中的高甘露糖和含有双分支 N-乙酰葡萄糖胺的聚糖减少。
在 CLBP 患者的血浆 N-聚糖水平上观察到的变化与慢性炎症中通常观察到的 N-糖基化变化一致。
据我们所知，这是第一项针对 CLBP 患者和血浆 N-聚糖组的大型临床研究，为潜在疾病病理学提供了新的糖组学视角。
