Proteomic Discovery of Stool Protein Biomarkers for Distinguishing Pediatric Inflammatory Bowel Disease Flares
Related Experiment Video
Updated: Jan 19, 2026
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Ellen Casavant1, K T Park2, Joshua E Elias3
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California.
Insights
Fecal calprotectin is a key marker for gut inflammation but has low specificity in children with inflammatory bowel disease (IBD). This study identified new protein biomarkers to improve diagnostic accuracy in pediatric IBD cases.
Area of Science:
- Gastroenterology
- Biomarker Discovery
- Pediatric Medicine
Background:
- Fecal calprotectin is a widely used biomarker for gut inflammation and diagnosing inflammatory bowel disease (IBD).
- While sensitive, fecal calprotectin exhibits lower specificity in pediatric patients, leading to potential misdiagnoses and delayed treatment.
- Improving diagnostic specificity is crucial for effective IBD monitoring in children.
Purpose of the Study:
- To identify novel protein biomarkers that can enhance the diagnostic specificity of fecal calprotectin for pediatric IBD.
- To develop a more accurate assay for monitoring IBD activity in pediatric populations.
Main Methods:
- A pilot study involving 10 pediatric patients with active IBD or in remission was conducted.
- Mass spectrometry-based proteomics was employed to analyze stool samples and quantify protein abundance.
- A panel of proteins with distinct abundance patterns between active IBD and remission was identified.
Main Results:
- Hundreds of stool proteins were identified and relatively quantified.
- At least 5 candidate proteins were prioritized for their potential to improve diagnostic accuracy.
- These proteins show promise in augmenting the negative predictive power of existing fecal biomarkers.
Conclusions:
- New protein biomarkers have been identified that may improve the specificity of IBD diagnosis in children.
- This discovery could lead to more accurate and timely diagnosis and treatment of pediatric IBD.
- Further validation is needed to integrate these biomarkers into clinical practice alongside fecal calprotectin.
Abstract:
Fecal calprotectin, the heterodimer of S100A8/S100A9, makes up ∼60% of neutrophil cytoplasmic protein content and is a canonical clinical biomarker of gut inflammation.1,2 Fecal calprotectin is commonly used to diagnose inflammatory bowel disease (IBD) and has an average sensitivity of 93% and specificity of 96%.1 For diagnosing pediatric IBD, calprotectin fecal tests have similar sensitivity (92%) but substantially less specificity (76%).1 Low specificity, especially in pediatric patients, means a high likelihood of false negative diagnoses, suggesting that a substantial number of active IBD cases remain undiagnosed and untreated. To improve on calprotectin as an effective IBD monitoring tool in pediatric populations, specificity must be increased. To develop an assay with higher specificity in pediatric patients, we identified a panel of multiple proteins that are present in both IBD flare and remission but have distinct abundance ranges between each condition. From a pilot cohort of 10 pediatric patients in states of either active disease or remission, we discovered and relatively quantified hundreds of stool proteins. Of these, our mass spectrometry-based study prioritized at least 5 that have potential to augment negative predictive power of mucosal-level inflammation alongside fecal biomarkers such as calprotectin.
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