Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn's Disease.

Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn's Disease.
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DOI:
10.3390/biom13060954
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发表时间:
2023-06-07
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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克罗恩病 (CD) 是一种消化道慢性炎症,严重损害患者的生活质量和福祉。抗 TNF 生物制剂彻底改变了 CD 的治疗,但许多患者对这种治疗没有充分的反应。先前的研究表明,与健康个体相比,CD 患者的免疫球蛋白 G (IgG) N-糖组的组成具有促炎模式。在这里,我们利用高通量 UHPLC 方法进行 N-聚糖分析,探讨抗 TNF 药物英夫利昔单抗和阿达木单抗对 198 名患者总血清 IgG N-糖组组成的纵向影响,以及基线 IgG N-聚糖的预测潜力,以检测 1315 名患者中抗 TNF 治疗的原发性无反应者。我们发现,在 14 周的抗 TNF 治疗期间,无论治疗反应如何,IgG 半乳糖基化显着减少,单半乳糖基化、双半乳糖基化和唾液酸化增加,所有这些都表明接受抗 TNF 治疗的 CD 患者的炎症环境有所减少。此外,我们观察到 IgG N-糖组在开始治疗之前可能包含有关抗 TNF 治疗结果的某些信息。然而,仅根据基线时的 IgG N-糖组组成来预测未来抗 TNF 治疗的主要无反应者是不可能的。
Crohn’s disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients’ quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline.
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