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A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease.

ABSTRACT: Introduction: Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. Therefore, novel predictive biomarkers are urgently needed that better reflect mucosal disease activity in IBD. The aim of this study was to identify a combination of serum inflammatory biomarkers predictive for endoscopic disease activity. Methods: Serum concentrations of 10 inflammatory biomarkers were analyzed in 118 IBD patients [64 Crohn's disease (CD), 54 ulcerative colitis (UC)] and 20 healthy controls. In a subset of 71 IBD patients, endoscopic disease activity was established. Non-parametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity. Results: Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A, and TNF-?) showed better prediction of IBD disease activity than routine measures (CRP, fecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8, and Eotaxin-1, showing an optimism-adjusted area under the ROC (AuROC) curve of 0.84 (95% CI: 0.73-0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43-0.72, P = 0.32). Conclusion: The combination of SAA, IL-6, IL-8, and Eotaxin-1 reliably predicts endoscopic disease activity in IBD and might be valuable for monitoring disease activity and management of the disease.

SUBMITTER: Bourgonje AR

PROVIDER: S-EPMC6849495 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease.

Bourgonje Arno R AR von Martels Julius Z H JZH Gabriëls Ruben Y RY Blokzijl Tjasso T Buist-Homan Manon M Heegsma Janette J Jansen Bernadien H BH van Dullemen Hendrik M HM Festen Eleonora A M EAM Ter Steege Rinze W F RWF Visschedijk Marijn C MC Weersma Rinse K RK de Vos Paul P Faber Klaas Nico KN Dijkstra Gerard G

Frontiers in medicine 20191105

<b>Introduction:</b> Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. Therefore, novel predictive biomarkers are urgently needed that better reflect mucosal disease activity in IBD. The aim of this study was to identify a combination of serum inflammatory biomarkers pr ...[more]

PMID: 31772929

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Project description:Inflammatory bowel diseases (IBDs) are chronic and progressive inflammatory disorders of the gastrointestinal tract. In IBD, protein serological biomarkers could be relevant tools for assessing disease activity, performing early-stage diagnosis and managing the treatment. Using the interleukin-10 knockout (IL-10(-/-)) mouse, a model that develops a time-dependent IBD-like disorder that predominates in the colon; we performed longitudinal studies of circulating protein biomarkers in IBD. Circulating protein profiles in serum samples collected from 30-, 93-, to 135-day-old IL-10(-/-) mice were investigated using two-dimensional differential gel electrophoresis and MALDI-TOF/TOF tandem mass spectrometry. A total of 15 different proteins were identified and confirmed by ELISA and Western blot to be differentially accumulated in serum samples from mid- to late-stage IL-10(-/-) mice compared to early non-inflamed IL-10(-/-) mice. The use of another model of colitis and an extra-intestinal inflammation model validated this biomarker panel and demonstrated that comprised some global inflammatory markers, some intestinal inflammation-specific markers and some chronic intestinal inflammation markers. Statistical analyses using misclassification error rate charts validated the use of these identified proteins as powerful biomarkers of colitis. Unlike standard biomarker screening studies, our analyses identified a panel of proteins that allowed the definition of protein signatures that reflect colitis status.Crohn's disease (CD) and ulcerative colitis (UC) are the most common inflammatory bowel diseases (IBDs) occurring in humans. The major current diagnosis tool is colonoscopy, which is invasive and could lead to false diagnosis. The emergence of serological biomarkers enables the use of new diagnosis tools such as protein signatures for IBD diagnosis/management. Using 2D-DIGE coupled to mass spectrometry, our longitudinal study in a mouse model of colitis identified a signature of protein biomarkers for specific stages of disease.

Dataset Information

A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease.

Publications

A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease.

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