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A novel diagnostic serum protein signature for pediatric inflammatory bowel disease
Charlotte Bache-Wiig Mathisen1,2, Niklas Nyström3, Igor Bazov4
1Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
Insights
Researchers identified a novel blood-based protein signature for pediatric inflammatory bowel disease (PIBD). This biomarker shows improved diagnostic accuracy over current methods, potentially simplifying PIBD diagnosis for children.
Area of Science:
- Pediatric Gastroenterology
- Biomarker Discovery
- Inflammatory Bowel Disease Diagnostics
Background:
- Diagnostic delay is a significant challenge in pediatric inflammatory bowel disease (PIBD).
- Fecal calprotectin (FCP) is a common biomarker but faces limitations due to sample collection difficulties.
- A reliable blood-based diagnostic marker is needed for efficient PIBD assessment.
Purpose of the Study:
- To identify and validate a blood-based protein signature for diagnosing PIBD in pediatric patients.
- To overcome the limitations associated with fecal sample collection for diagnostic markers.
- To develop a more accessible and accurate diagnostic tool for PIBD.
Main Methods:
- Utilized proximity extension assay to analyze plasma proteins in Swedish and Norwegian pediatric cohorts.
- Employed regularized logistic regression to identify a diagnostic protein signature.
- Assessed diagnostic performance using the area under the curve (AUC) with confidence intervals.
Main Results:
- A 31-protein signature differentiated PIBD from controls in the discovery cohort (AUC=0.83).
- A reduced signature, including hsCRP and seven other proteins, showed strong diagnostic capacity (AUC=0.85) in the validation cohort.
- The validated protein signature significantly outperformed high-sensitivity C-reactive protein (hsCRP) alone (p=0.006).
Conclusions:
- A validated blood-based protein signature for PIBD has been identified.
- This novel signature demonstrates superior diagnostic performance compared to hsCRP.
- Further assay development could integrate these biomarkers into clinical diagnostic pathways for PIBD.
Objectives:
Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood-based diagnostic protein signature of PIBD.
Methods:
Proteins were analyzed using proximity extension assay in plasma samples from treatment-naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population-based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs).
Results:
The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort (q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74-0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high-sensitivity C-reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78-0.92) outperforming hsCRP in the validation cohort (p = 0.006).
Conclusions:
We identified and validated a blood-based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD.
Trial Registration:
ClinicalTrials.gov identifier: NCT02727959.
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