Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases

Florent Clerc, Mislav Novokmet, Viktoria Dotz, Karli R. Reiding, Noortje de Haan, Guinevere S.M. Kammeijer, Hans Dalebout, Marco R. Bladergroen, Frano Vukovic, Erdmann Rapp, Stephan R. Targan, Gildardo Barron, Natalia Manetti, Anna Latiano, Dermot P.B. McGovern, Vito Annese, Gordan Lauc, Manfred Wuhrer, IBD BIOM consortium

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19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)829-843
Number of pages15
JournalGastroenterology
Volume155
Issue number3
DOIs
Publication statusPublished - 1 Sep 2018
Externally publishedYes

Keywords

  • Acute Phase Proteins
  • Immunoglobulins
  • MALDI-TOF-MS
  • Molecular Marker

Cite this

Clerc, F., Novokmet, M., Dotz, V., Reiding, K. R., de Haan, N., Kammeijer, G. S. M., Dalebout, H., Bladergroen, M. R., Vukovic, F., Rapp, E., Targan, S. R., Barron, G., Manetti, N., Latiano, A., McGovern, D. P. B., Annese, V., Lauc, G., Wuhrer, M., & IBD BIOM consortium (2018). Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases. Gastroenterology, 155(3), 829-843. https://doi.org/10.1053/j.gastro.2018.05.030