A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease Recurrence.

Bayes Theorem Biomarkers / metabolism Colonoscopy Crohn Disease / diagnosis Humans Ileum / pathology Receptors, CXCR3 Recurrence Retrospective Studies
CXCL9 Rutgeerts score biomarker

Journal

Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676

Informations de publication

Date de publication:
14 Jul 2022
Historique:
pubmed: 27 10 2021
medline: 19 7 2022
entrez: 26 10 2021
Statut: ppublish

Résumé

Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence. CD patients undergoing ICR were recruited across six centres. Serum samples were obtained at post-operative colonoscopy. A multiplex immunoassay was used to analyse 92 inflammation-related proteins [Olink Proteomics]. Bayesian analysis was used to identify proteins associated with increasing Rutgeerts score. Identified proteins were used in receiver operating characteristic [ROC] analysis to examine the ability to identify CD recurrence [Rutgeerts score ≥i2]. Existing single cell data were interrogated to further elucidate the role of the identified proteins. Data from 276 colonoscopies in 213 patients were available. Median time from surgery to first and second colonoscopy was 7 (interquartile range [IQR] 6-9) and 19 [IQR 16-23] months, respectively. Disease recurrence was evident at 60 [30%] first and 36 [49%] second colonoscopies. Of 14 proteins significantly associated with Rutgeerts score, the strongest signal was seen for CXCL9 and MMP1. Among patients on anti-tumour necrosis factor drugs, CXCL9 and CXCL11 were most strongly associated with Rutgeerts score. Both are CXCR3 ligands. Incorporation of identified proteins into ROC analysis improved the ability to identify disease recurrence as compared to C-reactive protein alone: area under the curve [AUC] 0.75 (95% confidence interval [CI]: 0.66-0.82] vs 0.64 [95% CI 0.56-0.72], p = 0.012. Single cell transcriptomic data provide evidence that innate immune cells are the primary source of the identified proteins. CXCR3 ligands are associated with CD recurrence following ICR. Incorporation of novel blood-based candidate biomarkers may aid in identification of CD recurrence.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence.
METHODS METHODS
CD patients undergoing ICR were recruited across six centres. Serum samples were obtained at post-operative colonoscopy. A multiplex immunoassay was used to analyse 92 inflammation-related proteins [Olink Proteomics]. Bayesian analysis was used to identify proteins associated with increasing Rutgeerts score. Identified proteins were used in receiver operating characteristic [ROC] analysis to examine the ability to identify CD recurrence [Rutgeerts score ≥i2]. Existing single cell data were interrogated to further elucidate the role of the identified proteins.
RESULTS RESULTS
Data from 276 colonoscopies in 213 patients were available. Median time from surgery to first and second colonoscopy was 7 (interquartile range [IQR] 6-9) and 19 [IQR 16-23] months, respectively. Disease recurrence was evident at 60 [30%] first and 36 [49%] second colonoscopies. Of 14 proteins significantly associated with Rutgeerts score, the strongest signal was seen for CXCL9 and MMP1. Among patients on anti-tumour necrosis factor drugs, CXCL9 and CXCL11 were most strongly associated with Rutgeerts score. Both are CXCR3 ligands. Incorporation of identified proteins into ROC analysis improved the ability to identify disease recurrence as compared to C-reactive protein alone: area under the curve [AUC] 0.75 (95% confidence interval [CI]: 0.66-0.82] vs 0.64 [95% CI 0.56-0.72], p = 0.012. Single cell transcriptomic data provide evidence that innate immune cells are the primary source of the identified proteins.
CONCLUSIONS CONCLUSIONS
CXCR3 ligands are associated with CD recurrence following ICR. Incorporation of novel blood-based candidate biomarkers may aid in identification of CD recurrence.

Identifiants

DOI: 10.1093/ecco-jcc/jjab186 PMID: 34698823 PMC: PMC9282882
pubmed: 34698823
pii: 6410738
doi: 10.1093/ecco-jcc/jjab186
pmc: PMC9282882
doi:

Substances chimiques

Biomarkers 0
CXCR3 protein, human 0
Receptors, CXCR3 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

900-910

Subventions

Organisme : NIDDK NIH HHS
ID : U01 DK062413
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK062429
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062432
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062429
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062422
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062423
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123758
Pays : United States
Organisme : NIH HHS
ID : U01 DK062420
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062420
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062431
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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Auteurs

Margaret Walshe (M)

Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
ORCID: 0000-0002-8696-354X

Shadi Nayeri (S)

Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.

Jiayi Ji (J)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Cristian Hernandez-Rocha (C)

Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.

Ksenija Sabic (K)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Liangyuan Hu (L)

Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Mamta Giri (M)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Shikha Nayar (S)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Steven Brant (S)

Crohn's and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Dermot P B McGovern (DPB)

F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.

John D Rioux (JD)

Research Centre, Montreal Heart Institute, Montréal, QC, Canada.
Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.

Richard H Duerr (RH)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA,USA.

Judy H Cho (JH)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Phil L Schumm (PL)

Department of Health Sciences, University of Chicago, Chicago, IL, USA.

Mark Lazarev (M)

Department of Gastroenterology, The John Hopkins Medical Institutions, Baltimore, MD,USA.

Mark S Silverberg (MS)

Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.

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