Clinical Report: Serum Proteomics Reveal a Continuous Spectrum in IBD Phenotypes
Overview
This multicenter study analyzed 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls, revealing distinct proteomic patterns that support a continuous spectrum of inflammatory bowel disease (IBD) rather than a strict Crohn’s disease (CD) versus ulcerative colitis (UC) dichotomy. Notably, colonic CD proteomic profiles were intermediate, resembling UC more closely than ileal CD.
Background
Inflammatory bowel disease encompasses heterogeneous chronic inflammatory disorders, primarily Crohn’s disease and ulcerative colitis, with overlapping clinical features and variable disease locations. Traditional classifications like the Montreal system stratify patients by disease location and behavior but do not fully capture molecular heterogeneity. Genetic and transcriptomic studies suggest an IBD continuum with ileal CD and UC at opposite ends, but these do not account for post-transcriptional modifications or environmental factors. Proteomic profiling of serum inflammatory proteins offers a promising approach to better characterize IBD subphenotypes and improve patient stratification.
Data Highlights
Group
Number of Subjects
Proteins Measured
IBD Patients
1551
86 inflammation-related serum proteins
Healthy Controls
312
86 inflammation-related serum proteins
Key Findings
Multiple serum proteins, including interleukin-17A, matrix metalloproteinase-10, and fibroblast growth factor-19, showed significant differential expression between ileal and colonic IBD (fold-change >1.2; FDR <0.05).
Multivariable models identified a protein signature positioning colonic CD between UC and ileal CD, supporting a continuous IBD spectrum.
Classification models differentiated UC from ileal CD with higher accuracy (median AUC > 0.73) than from colonic CD (median AUC < 0.62).
Models distinguishing colonic CD from ileal CD showed intermediate performance (median AUC 0.67–0.69), reflecting proteomic overlap.
Proteomic data suggest disease location may be a more relevant factor than traditional CD versus UC classification in defining IBD subtypes.
Clinical Implications
These findings highlight the importance of considering disease location and molecular heterogeneity in IBD management. Proteomic profiling could enhance patient stratification beyond conventional clinical classifications, potentially guiding personalized therapeutic strategies. Recognizing colonic CD as an intermediate phenotype may influence treatment decisions and clinical trial design by acknowledging the IBD continuum.
Conclusion
Serum proteomic analysis supports a continuous spectrum of IBD phenotypes with colonic CD bridging UC and ileal CD, challenging the traditional binary classification. Incorporating proteomic data may improve understanding and management of IBD heterogeneity.
References
Analysis of Serum Proteomics to Explore Heterogeneity in Inflammatory Bowel Disease: Findings from a Multicenter Investigation
by Benita Salomon, Padhmanand Sudhakar, Daniel Bergemalm, Erik Andersson, Olle Grännö, Marie Carlson, Charlotte R H Hedin, Johan D Söderholm, Lena Öhman, the COLLIBRI Consortium the BIO IBD Consortium, Ryan C Ungaro, Konrad Aden, Geert D’Haens, Mark S Silverberg, Sven Almer, Francesca Bresso, Adam Carstens, Mauro D’Amato, Carl Eriksson, Henrik Hjortswang, Åsa V Keita, Maria Ling Lundström, Maria K Magnusson, Jóhann P Hreinsson, Hans Strid, Carl Mårten Lindqvist, Robert Kruse, Dirk Repsilber, Bram Verstockt, Séverine Vermeire, Jonas Halfvarson
