Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10 000, Zagreb, Croatia.
Deparment of Cardiology, County Hospital Čakovec, Čakovec, Croatia.
J Transl Med. 2018 Nov 21;16(1):323. doi: 10.1186/s12967-018-1695-0.
Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls.
Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre.
Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development.
This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.
慢性阻塞性肺疾病（COPD）是一种复杂的疾病，其诊断需要进行肺量计评估。然而，考虑到其异质性，具有相似肺量计参数的患者不一定具有相同的功能状态。为了克服这一限制，人们已经研究了 COPD 的新型生物标志物。因此，我们旨在探索 N-糖链作为 COPD 生物标志物的潜在价值，并研究 COPD 患者和健康对照者血浆蛋白和免疫球蛋白 G（IgG）糖基化谱的个体变异。
我们对来自克罗地亚的 137 例 COPD 患者和 95 例匹配对照者的总血浆蛋白和 IgG N-糖组进行了分析。复制队列由另一家克罗地亚医疗中心招募的 61 例 COPD 患者和 148 例对照者组成。
COPD 患者的血浆蛋白 N-糖组显示低分支结构显著减少，相反，更复杂的糖结构（四半乳糖基化、三唾液酸化、四唾液酸化和触角岩藻糖化糖型）增加。我们还观察到血浆单半乳糖基化物质显著下降，这种变化在 IgG 糖组中也得到了复制。N-糖还具有区分不同 COPD GOLD 阶段患者的价值，随着疾病的进展，更复杂的糖结构的相对丰度增加。糖还与加重的频率存在统计学上的显著关联，并表明受吸烟影响，吸烟是 COPD 发展的主要危险因素。
这项研究表明，聚糖的复杂性与 COPD 相关，也反映了疾病的严重程度。此外，N-糖组的变化与加重频率相关，并受吸烟影响。总的来说，这项研究提供了 COPD 中血浆蛋白和 IgG N-糖组变化的新见解，并指出了疾病进展和严重程度的潜在新型标志物。
Zotero 插件
