Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Analyst. 2019 Mar 11;144(6):2042-2051. doi: 10.1039/c8an02014k.
Glycosylation is a post-translational modification essential for maintaining the structure and function of proteins. Abnormal N-glycan patterns have been found in various diseases compared to healthy controls. A decrease in terminal galactosylated N-glycans of serum IgG in rheumatoid arthritis (RA) and osteoarthritis (OA) may be involved in their immunopathogenesis. However, how glycan patterns differ between RA and OA remains unclear. Here, we identified 15 glycan forms of serum IgG from RA and OA using MALDI-TOF MS. We found that IgG galactosylation represented a suitable candidate for differentiating RA from healthy controls (AUC > 0.9). Then, we performed binary logistic regression to screen out three bisecting N-acetylglucosamine (GlcNAc) glycoforms for distinguishing between OA and RA. Combined ROC analysis of the selected glycans yielded an AUC of 0.81 between OA and RA and an AUC of 0.79 between OA and RF/ACPA negative RA. Similar results were found in the validation set. In conclusion, our analysis demonstrates that RA and OA are distinguished on the basis of their different IgG glycan patterns, which thus serve as suitable candidates as biomarkers for reliably identifying clinical conditions such as RA and OA.
糖基化是维持蛋白质结构和功能的一种重要的翻译后修饰。与健康对照组相比，各种疾病中都发现了异常的 N-糖型模式。类风湿关节炎 (RA) 和骨关节炎 (OA) 患者血清 IgG 末端半乳糖化 N-聚糖的减少可能与其免疫发病机制有关。然而，RA 和 OA 之间的糖型模式如何不同仍不清楚。在这里，我们使用 MALDI-TOF MS 从 RA 和 OA 患者的血清 IgG 中鉴定出 15 种糖型。我们发现 IgG 半乳糖基化是区分 RA 与健康对照组的合适候选者 (AUC > 0.9)。然后，我们进行了二项逻辑回归分析，以筛选出三种区分 OA 和 RA 的双分支 N-乙酰葡萄糖胺 (GlcNAc) 糖型。对选定糖型的联合 ROC 分析在 OA 和 RA 之间产生了 0.81 的 AUC，在 OA 和 RF/ACPA 阴性 RA 之间产生了 0.79 的 AUC。在验证集中也得到了类似的结果。总之，我们的分析表明，RA 和 OA 可以基于其不同的 IgG 糖型模式来区分，因此作为可靠识别 RA 和 OA 等临床状况的生物标志物具有很大的潜力。
