Distinct blood protein profiles associated with ileal and colonic ulcers in Crohn’s disease

Background and aims: Ileal and colonic Crohn’s disease (CD) are nowadays considered as two separate entities. In clinic, biologic treatments and biomarkers showed lower performance for ileal than colonic CD. In this context, we aim to: 1) characterise the systemic response associated with ileal and colonic CD; 2) explore serum biomarker candidates more specifically associated with ileal and colonic CD.
Methods: By combining different technologies (proximity extension assay, selected reaction monitoring and immunoturbidimetry for CRP), 207 serum proteins were measured in CD patients presenting no endoscopic lesions (endoscopic remission) (n=23), isolated ileal ulcers (n=17) or isolated colonic ulcers (n=16). The analysis was conducted using Wilcoxon-Mann-Whitney test and receiver operating characteristics (AUROC). The AUROC were compared using the bootstrap test (2000 replications).
Results: The presence of isolated ileal ulcers and isolated colonic ulcers were associated with the level of 6 and 18 serum proteins, respectively: (high: JUN, CNTNAP2; low: FCRL6, LTA, CLEC4A, NTF4); (high: CRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low: CLEC3B, GSN, TNFSF12, TPSAB1). CRP detected colonic and ileal ulcers with an AUROC of 0.77 (p-value=0.04) and 0.64 (p-value=0.07), respectively. The best combinations of markers for detecting ileal or colonic ulcers were respectively CLECA/LTA (AUROC=0.82, p-value vs CRP=0.06) or CRP/CSF3 (AUROC=0.85, p-value vs CRP=0.02).
Conclusion: In CD patients, ileal and colonic ulcers were associated with a distinct systemic response. CRP showed the capacity to detect patients with colonic but not ileal ulcers. Some markers might help to detect ileal ulcers or to improve the ability of CRP for detecting colonic ulcers.