Characterization of Inflammatory Bowel Disease Heterogeneity Using Serum Proteomics: A Multicenter Study

Area of Science:

• Molecular biology
• Immunology
• Gastroenterology

Background:

• Genetic and transcriptomic data necessitate improved molecular characterization of inflammatory bowel disease (IBD).
• Proteomics offers advanced insights into IBD phenotypes by capturing post-transcriptional modifications.

Purpose of the Study:

• To assess the inflammatory bowel disease (IBD) spectrum using serum proteins.
• To identify biological subtypes within IBD across European cohorts.

Main Methods:

• Measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 controls using proximity extension methodology.
• Screened for proteins with significantly different levels among IBD subtypes and between IBD and healthy controls.
• Employed classification models to explore the IBD spectrum based on probability scores for differentiating Crohn's disease (CD) and ulcerative colitis (UC).

Main Results:

• Multiple proteins differed significantly between ileal and colonic IBD.
• Identified a serum protein signature positioning colonic CD between UC and ileal CD on a continuous spectrum.
• Classification models differentiated UC from ileal CD (AUCs > 0.73) better than colonic CD (AUCs < 0.62), with intermediate performance for colonic versus ileal CD (AUCs 0.67-0.69).

Conclusions:

• Serum protein findings support a continuous IBD spectrum, challenging clear separation of CD and UC.
• Disease location, rather than CD versus UC, may define disease similarity, with colonic CD resembling UC more than ileal CD.