Institute of Molecular Pathology and Immunology of the University of Porto [IPATIMUP], Porto, Portugal.
Institute for Research and Innovation in Health [i3S], University of Porto, Porto, Portugal.
J Crohns Colitis. 2019 Jan 1;13(1):39-49. doi: 10.1093/ecco-jcc/jjy139.
There is a clinical need to identify biomarkers able to select patients who are most likely to develop aggressive/complicated disease, for early selection for appropriate therapy. Changes in the glycosylation profile of intestinal lymphocytic infiltrate were previously demonstrated to regulate T cell activity, being associated with disease severity in ulcerative colitis [UC] patients. We interrogated whether this heterogeneous expression of branched N-glycans in intestinal inflammatory infiltrate predicts therapy response early in disease course.
The expression levels of the branched N-glycans in colonic biopsies collected around time of diagnosis from a well-characterised cohort of 131 UC patients were correlated with response to standard therapy. Receiver operating characteristic analysis and specificity/sensitivity were determined.
Branched N-glycans levels around time of diagnosis predict non-response to conventional therapy with 75% specificity. Moreover, high levels of branched N-glycans predict 78% of UC patients who will display a favourable disease course [exclusively under 5-aminosalicylate therapy for more than 5 years of disease]. The best predictive performance was observed in severe UC patients with Mayo endoscopic subscore 3 and in those that were naïve to therapy. Multivariable analysis revealed that low levels of branched N-glycans and high levels of C-reactive protein [CRP] around time of diagnosis act as independent predictors of non-response to standard therapy. A powerful effect of the combined use of the branched N-glycans and CRP was observed.
Our results reveal a potential [glyco]biomarker that predicts, early in the disease course, patients who will fail to respond to standard therapy, benefiting thereby from other therapeutic strategies such as biologics.
临床上需要识别能够选择最有可能发展为侵袭性/复杂性疾病的患者的生物标志物，以便早期选择合适的治疗方法。先前已经证明，肠道淋巴细胞浸润的糖基化谱的变化能够调节 T 细胞活性，并与溃疡性结肠炎[UC]患者的疾病严重程度相关。我们探讨了肠道炎症浸润中这种分支 N-聚糖的异质性表达是否能在疾病早期预测治疗反应。
我们分析了 131 名 UC 患者的结肠活检样本中分支 N-聚糖的表达水平与标准治疗反应的相关性。我们通过接收者操作特征分析来确定特异性和敏感性。
诊断时分支 N-聚糖的水平可以预测对常规治疗的无反应，特异性为 75%。此外，高水平的分支 N-聚糖预测了 78%的 UC 患者将呈现出良好的疾病过程[仅在 5-氨基水杨酸治疗 5 年以上]。在 Mayo 内镜亚评分 3 的严重 UC 患者和未经治疗的患者中观察到最佳预测性能。多变量分析显示，诊断时分支 N-聚糖水平低和 C 反应蛋白[CRP]水平高是对标准治疗无反应的独立预测因子。观察到分支 N-聚糖和 CRP 联合使用的强大效果。
我们的研究结果揭示了一种潜在的[糖]生物标志物，它可以在疾病早期预测对标准治疗无反应的患者，从而使他们受益于其他治疗策略，如生物制剂。
