Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease. (17th November 2020)

• Record Type: Journal Article
• Authors: Kalla, R; Adams, A T; Bergemalm, D; Vatn, S; Kennedy, N A; Ricanek, P; Lindstrom, J; Ocklind, A; Hjelm, F; Ventham, N T; Ho, G T; Petren, C; Repsilber, D; Söderholm, J; Pierik, M; D'Amato, M; Gomollón, F; Olbjorn, C; Jahnsen, J; Vatn, M H; Halfvarson, J; Satsangi, J
• Is Part Of: Journal of Crohn's and colitis. Volume 15:Number 5(2021)
• Page Start: 699
• Page End: 708
• Publication Date: 2020-11-17
• Subjects: Crohn's disease -- proteins -- genetics -- inflammatory bowel diseases [IBD] -- ulcerative colitis -- OSM -- prognosis -- outcomes -- protein quantitative trait loci -- proximity extension assay; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjaa230
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. Methods: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. Results: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10 –23 ] and oncostatin-M [OSM; p = 3.7 × 10 –16 ]. Nine of these proteins are associated with cis -germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224–756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43–6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. Conclusion: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.