Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1002/jpn3.70379
Authors: Charlotte Bache‐Wiig Mathisen, Niklas Nyström, Igor Bazov, Ove Øyås, Manuela Zucknick, Svend Andersen, Christine Olbjørn, Gøri Perminow, Vendel A. Kristensen, Randi Opheim, Mauro D'Amato, Marie Carlson, Charlotte R. H. Hedin, Åsa V. Keita, Carl Mårten Lindqvist, Maria K. Magnusson, Samira Salihovic, Johan D. Söderholm, Lena Öhman, Robert Kruse, Dirk Repsilber, Jonas Halfvarson, Marte Lie Høivik
Institutions: Oslo University Hospital, University of Oslo, Uppsala University Hospital, University of Skövde, Sykehuset i Vestfold, Akershus University Hospital, Lovisenberg Diakonale Sykehus, Ikerbasque, Karolinska Institutet, CIC bioGUNE, Uppsala University, Karolinska University Hospital, Linköping University, Örebro University, University of Gothenburg
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,780
OpenAlex ID: W7129004507