Blood Protein Signature Diagnoses Pediatric IBD and Distinguishes Subtypes

Reliable, noninvasive blood tests remain an unmet need in routine evaluation. Differentiating Crohn's disease from ulcerative colitis is another critical challenge at presentation. A new study shows that a blood proteomic signature can identify pediatric IBD and distinguish its subtypes.

Researchers at Beth Israel Deaconess Medical Center (BIDMC) and Mass General Brigham for Children used large-scale blood proteomics to define distinct protein patterns associated with pediatric IBD. The approach culminated in a four‑protein signature intended for noninvasive diagnosis and subtype differentiation. Investigators aimed to enable differential diagnosis using routinely accessible assays.

In the discovery phase, the team measured the expression of roughly 1,300 circulating proteins and identified a disease‑associated pattern across children with and without IBD. Machine learning then narrowed this to eight proteins with strong diagnostic performance. The investigators further reduced the signal to four proteins and validated it using conventional, clinically available tests.

Samples came from an initial group of 47 children, followed by two larger cohorts of 295 and 105 children for validation. The four‑protein test identified IBD with high accuracy in the 80%–90% range. A separate four‑protein panel achieved more than 90% predictive performance for distinguishing ulcerative colitis from Crohn's disease.

The findings are published in eBioMedicine in a case–control study titled “Serum proteomics in paediatric inflammatory bowel disease from a case–control study: biomarker discovery and ulcerative colitis–Crohn's disease differentiation.” Beyond diagnostic utility, the protein patterns illuminated inflammatory pathways that differ between Crohn's disease and ulcerative colitis, which the authors note could inform future efforts toward targeted therapies and precision medicine approaches.

“Our findings measuring expression of 1,300 proteins in blood samples demonstrate the utility of blood proteomics in identifying disease-specific biomarkers and new noninvasive tests for differential diagnosis in pediatric IBD as well as defining the underlying pathophysiological mechanisms. A validated blood-based diagnostic approach could help reduce diagnostic delays, minimize invasive procedures, and support earlier, more personalized treatment decisions for children with IBD,” said co-senior author Towia Libermann, Ph.D., director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC.

“Noninvasive diagnostic tools can contribute to the diagnosis of inflammatory bowel disease but are not yet at the point of replacing standard clinical and pathologic data. Nevertheless, the data from these new proteomic platforms represent a much-needed advancement in the care of children with Crohn's disease and ulcerative colitis as we learn how best to not only treat diseases but also to personalize treatment,” said co-senior author Harland Winter, MD, co-director of the Center for Pediatric Inflammatory Bowel Disease at Mass General Brigham for Children.

Related Links
Beth Israel Deaconess Medical Center
Mass General Brigham for Children