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

Clerc, Florent; Novokmet, Mislav; Dotz, Viktoria; Reiding, Karli R.; Haan, Noortje de; Kammeijer, Guinevere S. M.; Dalebout, Hans; Bladergroen, Marco R.; Vukovic, Frano; Rapp, Erdmann; Satsangi, Jack; Nimmo, Elaine R.; Ventham, Nicholas T.; Drummond, Hazel E.; Kalla, Rahul; Adams, Alexander T.; O'Leary, Kate; Boyapati, Ray; Wilson, David C.; Merrick, Victoria; Campbell, Harry; Τheodoratou, Evropi; Rudan, Igor; Kennedy, Nicholas A.; Fernandes, Daryl L.; Spencer, Daniel I. R.; Gardner, Richard A.; Shubhakar, Archana; Urbanowicz, Paulina A.; Trbojević‐Akmačić, Irena; Krištić, Jasminka; Štambuk, Jerko; Pučić‐Baković, Maja; Vilaj, Marija; Pezer, Marija; Razdorov, Genadij; Šimurina, Mirna; Gornik, Olga; Biscaglia, Giuseppe; Palmieri, Orazio; Bossa, Fabrizio; D’Incà, R.; Danese, Silvio; Kohn, Anna; Pemberton, Iain K.; Kolarich, Daniel; Zoldoš, Vlatka; Aulchenko, Yurii S.; Pierik, Marieke; Jonkers, Daisy; Heuvel, Tim van den; Targan, Stephan R.; Barron, Gildardo; Manetti, Natalia; Latiano, Anna; McGovern, Dermot; Annese, Vito; Lauc, Gordan; Wuhrer, Manfred

doi:10.1053/j.gastro.2018.05.030

Cited by 76 publications

(83 citation statements)

References 55 publications

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“…Interestingly, IgG‐Fc fucosylation changes differed between UC and CD . Similarly, the bisection of fucosylated, sialylated glycans (A2FSB), which is mostly attributable to IgA, IgM, and possibly also IgG‐Fab glycans, was increased in CD, but not significantly affected in UC . A previous study on captured IgA1 was not able to find N‐ glycan associations with UC or CD in contrast to IgA O ‐glycosylation.…”

Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 74%

“…Strikingly, a detailed analysis of derived traits of sialylation revealed divergent associations with IBD: While α2,3‐sialylation was increased in di‐, tri‐, and tetraantennary structures, α2,6‐sialylation of tetraantennary glycans showed negative associations with disease (Fig. C).…”

Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 99%

“…Different medication regimens might have affected the disease associations in this case and should be considered in future studies on TPSNG disease markers. Similarly, the fucosylation of triantennary glycans, especially in glycans carrying two fucoses which are indicative of antennary fucosylation (A3F, A3Fa), differed in its association patterns with IBD between the discovery and replication cohorts .…”

Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 99%

“…Recently, these limitations have been addressed: Methods have been developed and validated allowing the analysis of larger sample sets in a robust and reproducible manner, facilitating the comparison of results between laboratories and disease‐specific cohorts . Notably, next to fluorescence detection of glycans, also methods with mass spectrometric detection have been proven suitable.…”

mentioning

confidence: 99%

“…Using these methods, glycomic signatures of various physiological parameters and human diseases have recently been described for human blood plasma and serum samples . Building on these studies, we here present human total plasma/serum N‐ glycome (TPSNG) signatures of major diseases and common disease risk factors.…”

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confidence: 99%

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N‐glycome signatures in human plasma: associations with physiology and major diseases

Dotz

Wuhrer

2019

FEBS Letters

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N‐glycome analysis in total plasma or serum yields information about the levels and glycosylation patterns of major plasma glycoproteins, including immunoglobulins, acute‐phase proteins, and apolipoproteins. Until recently, glycomic studies in disease settings largely suffered from small cohort sizes, poor analytical resolution, and poor comparability of results owing to the diversity of analytical techniques. Here, we report on recent advances in high‐throughput mass spectrometry glycomics technology that enabled elucidation of N‐glycome signatures in the plasma of patients with type 2 diabetes, inflammatory bowel disease, or colorectal cancer. Use of this technology revealed both commonalities and differences among disease fingerprints. Moreover, we summarize findings on glycomic signatures associated with age, sex, and body mass index. High‐throughput, high‐resolution glycomics technologies, together with robust data analysis workflows, will advance clinical translation.

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Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 74%

Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 99%

Section: N‐glycomic Signatures Of Major Human Diseasesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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N‐glycome signatures in human plasma: associations with physiology and major diseases

Dotz

Wuhrer

2019

FEBS Letters

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CE–MSApproaches for Glyco(proteo)mic Analysis

Wang¹,

Wang²,

Lageveen-Kammeijer³

2022

Capillary Electrophoresis‐Mass Spectrometry for Proteomics and Metabolomics

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Validation of diagnostic and predictive biomarkers for hereditary angioedema via plasma N‐glycomics

Zhang

Wang

et al. 2021

Clinical & Translational All

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Background Hereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N‐glycomes are disease‐specific and have great potential for the discovery of non‐invasive biomarkers. In this study, we profiled the plasma N‐glycome of HAE patients from two independent cohorts to identify candidate biomarkers. Methods Linkage‐specific sialylation derivatization combined with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry detection and automated data processing was employed to analyze the plasma N‐glycome of two independent type‐1 HAE cohorts. Results HAE patients had abnormal glycan complexity, galactosylation, and α2,3‐ and α2,6‐linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort. Conclusions We reported the full plasma N‐glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein‐specific and prospective studies are needed to validate our findings.

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

Abstract: 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.

Cited by 76 publications

References 55 publications

N‐glycome signatures in human plasma: associations with physiology and major diseases

N‐glycome signatures in human plasma: associations with physiology and major diseases

CE–MSApproaches for Glyco(proteo)mic Analysis

Validation of diagnostic and predictive biomarkers for hereditary angioedema via plasma N‐glycomics

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