PMID- 34698823
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20230501
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Print)
IS  - 1873-9946 (Linking)
VI  - 16
IP  - 6
DP  - 2022 Jul 14
TI  - A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease 
      Recurrence.
PG  - 900-910
LID - 10.1093/ecco-jcc/jjab186 [doi]
AB  - BACKGROUND AND AIMS: Crohn's disease [CD] recurrence following ileocolic 
      resection [ICR] is common. We sought to identify blood-based biomarkers 
      associated with CD recurrence. 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: 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: CXCR3 ligands are 
      associated with CD recurrence following ICR. Incorporation of novel blood-based 
      candidate biomarkers may aid in identification of CD recurrence.
CI  - (c) 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.
FAU - Walshe, Margaret
AU  - Walshe M
AUID- ORCID: 0000-0002-8696-354X
AD  - Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, 
      Sinai Health System, Toronto, Ontario, Canada.
AD  - Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Nayeri, Shadi
AU  - Nayeri S
AD  - Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, 
      Sinai Health System, Toronto, Ontario, Canada.
FAU - Ji, Jiayi
AU  - Ji J
AD  - Department of Population Health Science and Policy, Icahn School of Medicine at 
      Mount Sinai, New York, NY, USA.
AD  - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 
      NY, USA.
FAU - Hernandez-Rocha, Cristian
AU  - Hernandez-Rocha C
AD  - Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, 
      Sinai Health System, Toronto, Ontario, Canada.
AD  - Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Sabic, Ksenija
AU  - Sabic K
AD  - The Charles Bronfman Institute for Personalized Medicine, Icahn School of 
      Medicine at Mount Sinai, New York, NY, USA.
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Hu, Liangyuan
AU  - Hu L
AD  - Department of Population Health Science and Policy, Icahn School of Medicine at 
      Mount Sinai, New York, NY, USA.
AD  - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 
      NY, USA.
FAU - Giri, Mamta
AU  - Giri M
AD  - The Charles Bronfman Institute for Personalized Medicine, Icahn School of 
      Medicine at Mount Sinai, New York, NY, USA.
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Nayar, Shikha
AU  - Nayar S
AD  - The Charles Bronfman Institute for Personalized Medicine, Icahn School of 
      Medicine at Mount Sinai, New York, NY, USA.
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Brant, Steven
AU  - Brant S
AD  - 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.
FAU - McGovern, Dermot P B
AU  - McGovern DPB
AD  - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, 
      Cedars Sinai Medical Center, Los Angeles, CA, USA.
FAU - Rioux, John D
AU  - Rioux JD
AD  - Research Centre, Montreal Heart Institute, Montreal, QC, Canada.
AD  - Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada.
FAU - Duerr, Richard H
AU  - Duerr RH
AD  - Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, 
      Pittsburgh, PA,USA.
FAU - Cho, Judy H
AU  - Cho JH
AD  - The Charles Bronfman Institute for Personalized Medicine, Icahn School of 
      Medicine at Mount Sinai, New York, NY, USA.
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Schumm, Phil L
AU  - Schumm PL
AD  - Department of Health Sciences, University of Chicago, Chicago, IL, USA.
FAU - Lazarev, Mark
AU  - Lazarev M
AD  - Department of Gastroenterology, The John Hopkins Medical Institutions, Baltimore, 
      MD,USA.
FAU - Silverberg, Mark S
AU  - Silverberg MS
AD  - Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, 
      Sinai Health System, Toronto, Ontario, Canada.
AD  - Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, 
      University of Toronto, Toronto, Ontario, Canada.
LA  - eng
GR  - U01 DK062413/DK/NIDDK NIH HHS/United States
GR  - U24 DK062429/DK/NIDDK NIH HHS/United States
GR  - U01 DK062432/DK/NIDDK NIH HHS/United States
GR  - U01 DK062429/DK/NIDDK NIH HHS/United States
GR  - U01 DK062422/DK/NIDDK NIH HHS/United States
GR  - U01 DK062423/DK/NIDDK NIH HHS/United States
GR  - R01 DK123758/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420/NH/NIH HHS/United States
GR  - U01 DK062420/DK/NIDDK NIH HHS/United States
GR  - U01 DK062431/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Biomarkers)
RN  - 0 (CXCR3 protein, human)
RN  - 0 (Receptors, CXCR3)
SB  - IM
MH  - Bayes Theorem
MH  - Biomarkers/metabolism
MH  - Colonoscopy
MH  - *Crohn Disease/diagnosis/metabolism/surgery
MH  - Humans
MH  - Ileum/pathology
MH  - Receptors, CXCR3
MH  - Recurrence
MH  - Retrospective Studies
PMC - PMC9282882
OTO - NOTNLM
OT  - CXCL9
OT  - Rutgeerts score
OT  - biomarker
EDAT- 2021/10/27 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/10/26
CRDT- 2021/10/26 12:27
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2021/10/26 12:27 [entrez]
PHST- 2022/10/26 00:00 [pmc-release]
AID - 6410738 [pii]
AID - jjab186 [pii]
AID - 10.1093/ecco-jcc/jjab186 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2022 Jul 14;16(6):900-910. doi: 10.1093/ecco-jcc/jjab186.