1. Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases
- Author
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Viktoria Dotz, Stephan R. Targan, Hazel E. Drummond, Gildardo Barron, Daisy Jonkers, Daniel Kolarich, Tim van den Heuvel, Gordan Lauc, David C. Wilson, Elaine R. Nimmo, Marco R. Bladergroen, Frano Vukovic, Manfred Wuhrer, Nicholas A. Kennedy, Hans Dalebout, Karli R. Reiding, Alex Adams, Iain K. Pemberton, Daryl L. Fernandes, Vito Annese, Maja Pučić-Baković, Fabrizio Bossa, Silvio Danese, Genadij Razdorov, Rahul Kalla, Irena Trbojević-Akmačić, Victoria Merrick, Igor Rudan, Evropi Theodoratou, Ray Boyapati, Nicholas T. Ventham, Noortje de Haan, Richard A. Gardner, Florent Clerc, Harry Campbell, Jasminka Krištić, Erdmann Rapp, Jerko Štambuk, Dermot P.B. McGovern, Mirna Šimurina, Natalia Manetti, Archana Shubhakar, Anna Kohn, Jack Satsangi, Paulina A. Urbanowicz, Marieke Pierik, Guinevere S. M. Kammeijer, Vlatka Zoldoš, Orazio Palmieri, Mislav Novokmet, Yurii S. Aulchenko, Renata D'Incà, Daniel I. R. Spencer, KR O’Leary, Olga Gornik, Marija Vilaj, Anna Latiano, Giuseppe Biscaglia, and Marija Pezer
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Glycosylation ,Immunoglobulins ,Gastroenterology ,Inflammatory bowel disease ,Acute Phase Proteins ,MALDI-TOF-MS ,Molecular Marker ,03 medical and health sciences ,Crohn Disease ,Polysaccharides ,Internal medicine ,medicine ,Humans ,Fucosylation ,Crohn's disease ,Hepatology ,biology ,business.industry ,C-reactive protein ,Acute-phase protein ,Case-control study ,Middle Aged ,medicine.disease ,Ulcerative colitis ,carbohydrates (lipids) ,030104 developmental biology ,Logistic Models ,Case-Control Studies ,Cohort ,biology.protein ,Disease Progression ,Colitis, Ulcerative ,Female ,business ,Protein Processing, Post-Translational ,Biomarkers - Abstract
Background & Aims Biomarkers are needed for early detection of Crohn’s disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex posttranslational modification of proteins that affects their structure and activity. We compared plasma N-glycosylation profiles between patients with CD or UC and healthy individuals (controls). Methods We analyzed the total plasma N-glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique. Plasma samples were acquired from 2 hospitals in Italy (discovery cohort, 1989 patients with inflammatory bowel disease [IBD] and 570 controls) and 1 medical center in the United States (validation cohort, 646 cases of IBD and 426 controls). Sixty-three glycoforms met our criteria for relative quantification and were extracted from the raw data with the software MassyTools. Common features shared by the glycan compositions were combined in 78 derived traits, including the number of antennae of complex-type glycans and levels of fucosylation, bisection, galactosylation, and sialylation. Associations of plasma N-glycomes with age, sex, CD, UC, and IBD-related parameters such as disease location, surgery and medication, level of C-reactive protein, and sedimentation rate were tested by linear and logistic regression. Results Plasma samples from patients with IBD had a higher abundance of large-size glycans compared with controls, a decreased relative abundance of hybrid and high-mannose structures, lower fucosylation, lower galactosylation, and higher sialylation (α2,3- and α2,6-linked). We could discriminate plasma from patients with CD from that of patients with UC based on higher bisection, lower galactosylation, and higher sialylation (α2,3-linked). Glycosylation patterns were associated with disease location and progression, the need for a more potent medication, and surgery. These results were replicated in a large independent cohort. Conclusions We performed high-throughput analysis to compare total plasma N-glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients’ responses to treatment.
- Published
- 2017