A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients
A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients
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DOI：
10.1093/ecco-jcc/jjy139
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Pinho, Salome S.
中科院分区：
文献类型：
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作者：
Pereira, Marcia S.;Maia, Luis;Pinho, Salome S.
背景和目标：临床上需要鉴定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，用于早期选择适当的治疗。肠淋巴细胞浸润的糖基化谱的变化先前被证明可调节T细胞活性，与溃疡性结肠炎[UC]患者的疾病严重程度相关。我们询问这种异质性表达的分支N-聚糖在肠道炎症浸润预测治疗反应早期疾病course.Methods：在结肠活检组织中收集的分支N-聚糖的表达水平，从一个良好的特征队列的131例UC患者的诊断时间与标准治疗的反应。受试者工作特性分析和特异性/灵敏度determined.Results：诊断时左右的分支N-聚糖水平预测无反应的常规治疗与75%的特异性。此外，高水平的分支N-聚糖预测78%的UC患者将显示有利的病程[仅在5-氨基水杨酸治疗超过5年的疾病]。在马约内镜分项评分3的重度UC患者和未接受过治疗的患者中观察到最佳预测性能。多变量分析显示，诊断时低水平的分支N-聚糖和高水平的C-反应蛋白[CRP]是对标准治疗无反应的独立预测因素。一个强大的效果的组合使用的分支N-聚糖和CRP observed.Conclusions：我们的研究结果揭示了一个潜在的[糖]生物标志物，预测，早期的疾病过程中，患者谁将无法响应标准治疗，从而受益于其他治疗策略，如生物制剂。
Background and Aims: 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.Methods: 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.Results: 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 naive 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.Conclusions: 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.