Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Postbus 9600, Leiden 2300 RC, The Netherlands.
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht 3584 CH, The Netherlands.
J Proteome Res. 2023 Oct 6;22(10):3213-3224. doi: 10.1021/acs.jproteome.3c00260. Epub 2023 Aug 28.
Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA and -glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care.
炎症性肠病(IBD),如克罗恩病(CD)和溃疡性结肠炎(UC),是一种消化道的慢性复发性炎症,其发病率不断上升,但病因不明,也无法治愈。CD 和 UC 的症状相似,但对手术和药物的反应不同。目前的诊断工具通常涉及侵入性程序,而缺乏用于患者分层的实验室标志物。对免疫球蛋白 G 和总血浆糖基化的大型糖组学研究表明,IBD 具有生物标志物的潜力,可帮助确定疾病机制和治疗选择。迄今为止,在 IBD 背景下,肠粘液中分泌的重要免疫球蛋白——免疫球蛋白 A 的糖基化特征仍未确定。我们的研究通过胰蛋白酶糖肽的反相液相色谱-电喷雾电离质谱法,在 442 例 IBD 病例(188 例 CD 和 254 例 UC)和 120 例健康对照中研究了免疫球蛋白 A1 和 A2 糖基化与 IBD 的关联。患者组之间 IgA 和 -糖基化(包括半乳糖基化、二分法、唾液酸化和天线分支)的差异与疾病有关,这些发现导致构建了一个统计模型,无需侵入性程序即可预测患者的疾病组。这项研究扩展了我们对 CD 和 UC 的现有认识,并有助于开发非侵入性生物标志物和更好的患者护理。