Margaret Walshe1,2, Shadi Nayeri1, Jiayi Ji3,4, Cristian Hernandez-Rocha1,2, Ksenija Sabic5,6, Liangyuan Hu3,4, Mamta Giri5,6, Shikha Nayar5,6, Steven Brant7, Dermot P B McGovern8, John D Rioux9,10, Richard H Duerr11, Judy H Cho5,6, Phil L Schumm12, Mark Lazarev13, Mark S Silverberg1,2. 1. Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. 2. Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada. 3. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. 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. 8. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA. 9. Research Centre, Montreal Heart Institute, Montréal, QC, Canada. 10. Faculty of Medicine, Université de Montréal, Montréal, QC, Canada. 11. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA,USA. 12. Department of Health Sciences, University of Chicago, Chicago, IL, USA. 13. Department of Gastroenterology, The John Hopkins Medical Institutions, Baltimore, MD,USA.
Abstract
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.
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.
Authors: P Maerten; B S Kwon; C Shen; G De Hertogh; P Cadot; D M A Bullens; L Overbergh; C Mathieu; G Van Assche; K Geboes; P Rutgeerts; J L Ceuppens Journal: Clin Exp Immunol Date: 2006-02 Impact factor: 4.330
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Authors: S Hosomi; N Oshitani; N Kamata; M Sogawa; H Okazaki; T Tanigawa; H Yamagami; K Watanabe; K Tominaga; T Watanabe; Y Fujiwara; K Maeda; K Hirakawa; T Arakawa Journal: Clin Exp Immunol Date: 2010-11-19 Impact factor: 4.330