Emerging biomarkers in inflammatory bowel disease (embark) study identifies fecal calprotectin, serum mmp9, and serum il-22 as a novel combination of biomarkers for crohn's disease activity: Role of cross-sectional imaging

William Alvis Faubion, Joel Garland Fletcher, Sharon O'Byrne, Brian G. Feagan, Willem Js De Villiers, Bruce Salzberg, Scott Plevy, Deborah D. Proctor, John F. Valentine, Peter D. Higgins, Jeffrey M. Harris, Lauri Diehl, Lilyan Wright, Gaik Wei Tew, Diana Luca, Karen Basu, Mary E. Keir

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Objectives:In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery.Methods:UC (n=107) and CD (n=157) patients were characterized and underwent ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist and radiologist who incorporated findings of inflammation into a single score (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers were evaluated for association with the Mayo Clinic endoscopy score in UC patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with a moderate degree of correlation (P≤0.3) were evaluated using multivariate analysis with model selection using a stepwise procedure.Results:In UC, ordinal logistic regression using Mayo Clinic endoscopy subscore selected the combination of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudo R 2 =0.353). In CD, we found that use of the ICO-CTE increased specificity of known biomarkers. Using ICO-CTE as the dependent variable for biomarker discovery, the selected biomarkers were the combination of fecal calprotectin, serum MMP9, and serum IL-22 (r=0.699).Conclusions:Incorporation of both ICO and CTE into a single measure increased biomarker performance in CD. Combinations of fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin, serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest association with imaging/endoscopy-defined inflammation.

Original languageEnglish (US)
Pages (from-to)1891-1900
Number of pages10
JournalAmerican Journal of Gastroenterology
Volume108
Issue number12
DOIs
StatePublished - Dec 2013

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Leukocyte L1 Antigen Complex
Inflammatory Bowel Diseases
Crohn Disease
Biomarkers
Tomography
Ulcerative Colitis
Serum
Endoscopy
Inflammation
Matrix Metalloproteinase 9
Multivariate Analysis
Logistic Models

ASJC Scopus subject areas

  • Gastroenterology

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Emerging biomarkers in inflammatory bowel disease (embark) study identifies fecal calprotectin, serum mmp9, and serum il-22 as a novel combination of biomarkers for crohn's disease activity : Role of cross-sectional imaging. / Faubion, William Alvis; Fletcher, Joel Garland; O'Byrne, Sharon; Feagan, Brian G.; De Villiers, Willem Js; Salzberg, Bruce; Plevy, Scott; Proctor, Deborah D.; Valentine, John F.; Higgins, Peter D.; Harris, Jeffrey M.; Diehl, Lauri; Wright, Lilyan; Tew, Gaik Wei; Luca, Diana; Basu, Karen; Keir, Mary E.

In: American Journal of Gastroenterology, Vol. 108, No. 12, 12.2013, p. 1891-1900.

Research output: Contribution to journalArticle

Faubion, WA, Fletcher, JG, O'Byrne, S, Feagan, BG, De Villiers, WJ, Salzberg, B, Plevy, S, Proctor, DD, Valentine, JF, Higgins, PD, Harris, JM, Diehl, L, Wright, L, Tew, GW, Luca, D, Basu, K & Keir, ME 2013, 'Emerging biomarkers in inflammatory bowel disease (embark) study identifies fecal calprotectin, serum mmp9, and serum il-22 as a novel combination of biomarkers for crohn's disease activity: Role of cross-sectional imaging', American Journal of Gastroenterology, vol. 108, no. 12, pp. 1891-1900. https://doi.org/10.1038/ajg.2013.354
Faubion, William Alvis ; Fletcher, Joel Garland ; O'Byrne, Sharon ; Feagan, Brian G. ; De Villiers, Willem Js ; Salzberg, Bruce ; Plevy, Scott ; Proctor, Deborah D. ; Valentine, John F. ; Higgins, Peter D. ; Harris, Jeffrey M. ; Diehl, Lauri ; Wright, Lilyan ; Tew, Gaik Wei ; Luca, Diana ; Basu, Karen ; Keir, Mary E. / Emerging biomarkers in inflammatory bowel disease (embark) study identifies fecal calprotectin, serum mmp9, and serum il-22 as a novel combination of biomarkers for crohn's disease activity : Role of cross-sectional imaging. In: American Journal of Gastroenterology. 2013 ; Vol. 108, No. 12. pp. 1891-1900.
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abstract = "Objectives:In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery.Methods:UC (n=107) and CD (n=157) patients were characterized and underwent ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist and radiologist who incorporated findings of inflammation into a single score (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers were evaluated for association with the Mayo Clinic endoscopy score in UC patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with a moderate degree of correlation (P≤0.3) were evaluated using multivariate analysis with model selection using a stepwise procedure.Results:In UC, ordinal logistic regression using Mayo Clinic endoscopy subscore selected the combination of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudo R 2 =0.353). In CD, we found that use of the ICO-CTE increased specificity of known biomarkers. Using ICO-CTE as the dependent variable for biomarker discovery, the selected biomarkers were the combination of fecal calprotectin, serum MMP9, and serum IL-22 (r=0.699).Conclusions:Incorporation of both ICO and CTE into a single measure increased biomarker performance in CD. Combinations of fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin, serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest association with imaging/endoscopy-defined inflammation.",
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AU - Faubion, William Alvis

AU - Fletcher, Joel Garland

AU - O'Byrne, Sharon

AU - Feagan, Brian G.

AU - De Villiers, Willem Js

AU - Salzberg, Bruce

AU - Plevy, Scott

AU - Proctor, Deborah D.

AU - Valentine, John F.

AU - Higgins, Peter D.

AU - Harris, Jeffrey M.

AU - Diehl, Lauri

AU - Wright, Lilyan

AU - Tew, Gaik Wei

AU - Luca, Diana

AU - Basu, Karen

AU - Keir, Mary E.

PY - 2013/12

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N2 - Objectives:In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery.Methods:UC (n=107) and CD (n=157) patients were characterized and underwent ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist and radiologist who incorporated findings of inflammation into a single score (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers were evaluated for association with the Mayo Clinic endoscopy score in UC patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with a moderate degree of correlation (P≤0.3) were evaluated using multivariate analysis with model selection using a stepwise procedure.Results:In UC, ordinal logistic regression using Mayo Clinic endoscopy subscore selected the combination of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudo R 2 =0.353). In CD, we found that use of the ICO-CTE increased specificity of known biomarkers. Using ICO-CTE as the dependent variable for biomarker discovery, the selected biomarkers were the combination of fecal calprotectin, serum MMP9, and serum IL-22 (r=0.699).Conclusions:Incorporation of both ICO and CTE into a single measure increased biomarker performance in CD. Combinations of fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin, serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest association with imaging/endoscopy-defined inflammation.

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