医学
炎症性肠病
溃疡性结肠炎
克罗恩病
胃肠病学
内科学
炎症性肠病
蛋白质组学
曲线下面积
疾病
免疫学
基因
生物
遗传学
作者
B Salomon,Padhmanand Sudhakar,Daniel Bergemalm,Erik Andersson,Olle Grännö,Marie Carlson,Charlotte Hedin,Johan D. Söderholm,Lena Öhman,C. Lindqvist,Robert Kruse,Dirk Repsilber,Bram Verstockt,Séverine Vermeire,Jonas Halfvarson
出处
期刊:Journal of Crohn's and Colitis
[Oxford University Press]
日期:2024-11-04
标识
DOI:10.1093/ecco-jcc/jjae169
摘要
Abstract Background Recent genetic and transcriptomic data highlight the need for improved molecular characterisation of inflammatory bowel disease (IBD). Proteomics may advance the delineation of IBD phenotypes since it accounts for post-transcriptional modifications. Aim We aimed to assess the IBD spectrum based on inflammatory serum proteins and identify discriminative patterns of underlying biological subtypes across multiple European cohorts. Methods Using proximity extension methodology, we measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls (HC). We screened for proteins exhibiting significantly different levels among IBD subtypes and between IBD and HC. Classification models for differentiating between Crohn's disease (CD) and ulcerative colitis (UC) were employed to explore the IBD spectrum based on estimated probability scores. Results Levels of multiple proteins, such as IL-17A, MMP-10, and FGF-19, differed (fold-change>1.2; FDR<0.05) between ileal vs colonic IBD. Using multivariable models, a protein signature reflecting the IBD spectrum was identified, positioning colonic CD between UC and ileal CD, which were at opposite ends of the spectrum. Based on area under the curve (AUC) estimates, classification models more accurately differentiated UC from ileal CD (median AUCs>0.73) than colonic CD (median AUCs<0.62). Models differentiating colonic CD from ileal CD demonstrated intermediate performance (median AUCs 0.67-0.69). Conclusion Our findings in serum proteins support the presence of a continuous IBD spectrum rather than a clear separation of CD and UC. Within the spectrum, disease location may reflect a more similar disease than CD vs UC, as colonic CD resembled UC more closely than ileal CD.
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