Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

Archana Shubhakar; Bas C. Jansen; Alex T. Adams; Karli R. Reiding; Nicholas T. Ventham; Rahul Kalla; Daniel Bergemalm; Paulina A. Urbanowicz; Richard A. Gardner; Manfred Wuhrer; Jonas Halfvarson; Jack Satsangi; Daryl L. Fernandes; Daniel I.R. Spencer

doi:10.1093/ecco-jcc/jjad012

Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

Archana Shubhakar^*, Bas C. Jansen, Alex T. Adams, Karli R. Reiding, Nicholas T. Ventham, Rahul Kalla, Daniel Bergemalm, Paulina A. Urbanowicz, Richard A. Gardner, Manfred Wuhrer, Jonas Halfvarson, Jack Satsangi, Daryl L. Fernandes, Daniel I.R. Spencer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.

Original language	English
Pages (from-to)	919-932
Number of pages	14
Journal	Journal of Crohn's and Colitis
Volume	17
Issue number	6
Early online date	24 Jan 2023
DOIs	https://doi.org/10.1093/ecco-jcc/jjad012
Publication status	Published - 1 Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.

Funding

The work was supported by EU FP7 grants: European Commission IBD-BIOM [Grant number # 305479] and IBD-CHARACTER [Grant number # 2858546].

Funders	Funder number
European Commission IBD-BIOM	305479
IBD-CHARACTER	2858546
Seventh Framework Programme

Keywords

biomarker
Crohn's disease
N-Glycans
personalised treatment
prognosis
ulcerative colitis

Access to Document

10.1093/ecco-jcc/jjad012

jjad012Final published version, 6.74 MBLicence: Taverne

Cite this

Shubhakar, A., Jansen, B. C., Adams, A. T., Reiding, K. R., Ventham, N. T., Kalla, R., Bergemalm, D., Urbanowicz, P. A., Gardner, R. A., Wuhrer, M., Halfvarson, J., Satsangi, J., Fernandes, D. L., & Spencer, D. I. R. (2023). Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease. Journal of Crohn's and Colitis, 17(6), 919-932. https://doi.org/10.1093/ecco-jcc/jjad012

@article{12c4789c98f5493e8f9a73289d648b02,

title = "Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease",

abstract = "Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.",

keywords = "biomarker, Crohn's disease, N-Glycans, personalised treatment, prognosis, ulcerative colitis",

author = "Archana Shubhakar and Jansen, {Bas C.} and Adams, {Alex T.} and Reiding, {Karli R.} and Ventham, {Nicholas T.} and Rahul Kalla and Daniel Bergemalm and Urbanowicz, {Paulina A.} and Gardner, {Richard A.} and Manfred Wuhrer and Jonas Halfvarson and Jack Satsangi and Fernandes, {Daryl L.} and Spencer, {Daniel I.R.}",

year = "2023",

month = jun,

day = "1",

doi = "10.1093/ecco-jcc/jjad012",

language = "English",

volume = "17",

pages = "919--932",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Oxford University Press",

number = "6",

}

Shubhakar, A, Jansen, BC, Adams, AT, Reiding, KR, Ventham, NT, Kalla, R, Bergemalm, D, Urbanowicz, PA, Gardner, RA, Wuhrer, M, Halfvarson, J, Satsangi, J, Fernandes, DL & Spencer, DIR 2023, 'Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease', Journal of Crohn's and Colitis, vol. 17, no. 6, pp. 919-932. https://doi.org/10.1093/ecco-jcc/jjad012

TY - JOUR

T1 - Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

AU - Shubhakar, Archana

AU - Jansen, Bas C.

AU - Adams, Alex T.

AU - Reiding, Karli R.

AU - Ventham, Nicholas T.

AU - Kalla, Rahul

AU - Bergemalm, Daniel

AU - Urbanowicz, Paulina A.

AU - Gardner, Richard A.

AU - Wuhrer, Manfred

AU - Halfvarson, Jonas

AU - Satsangi, Jack

AU - Fernandes, Daryl L.

AU - Spencer, Daniel I.R.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.

AB - Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.

KW - biomarker

KW - Crohn's disease

KW - N-Glycans

KW - personalised treatment

KW - prognosis

KW - ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=85159095357&partnerID=8YFLogxK

U2 - 10.1093/ecco-jcc/jjad012

DO - 10.1093/ecco-jcc/jjad012

M3 - Article

C2 - 36694402

AN - SCOPUS:85159095357

SN - 1873-9946

VL - 17

SP - 919

EP - 932

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 6

ER -

Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this