Characterisation of IBD heterogeneity using serum proteomics: A multicentre study.

Benita Salomon, Padhmanand Sudhakar, Daniel Bergemalm, Erik Andersson, Olle Grännö, Marie Carlson, Charlotte R H Hedin, Johan D Söderholm, Lena Öhman, Carl Mårten Lindqvist, Robert Kruse, Dirk Repsilber, Bram Verstockt, Séverine Vermeire, Jonas Halfvarson
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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.

利用血清蛋白质组学描述 IBD 的异质性:一项多中心研究
背景:最新的遗传学和转录组数据突显了改善炎症性肠病(IBD)分子特征的必要性。目的:我们的目的是根据炎症性血清蛋白评估 IBD 病谱,并在多个欧洲队列中确定潜在生物亚型的鉴别模式:方法:我们使用近似延伸方法测量了 1551 例 IBD 患者和 312 例健康对照(HC)的 86 种炎症相关血清蛋白。我们筛选了在 IBD 亚型之间以及 IBD 和 HC 之间表现出明显不同水平的蛋白质。我们采用了区分克罗恩病(CD)和溃疡性结肠炎(UC)的分类模型,根据估计的概率分数来探索 IBD 病谱:结果:IL-17A、MMP-10 和 FGF-19 等多种蛋白质的水平与结肠 CD(中位数 AUCs)相比存在差异(折叠变化>1.2;FDR0.73):我们对血清蛋白的研究结果表明,IBD存在一个连续的谱系,而不是CD和UC的明显分界。在该谱系中,疾病位置可能反映了比 CD 与 UC 更相似的疾病,因为结肠 CD 比回肠 CD 更接近 UC。
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