Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Gut. 2023 Jul;72(7):1271-1287. doi: 10.1136/gutjnl-2021-326451. Epub 2022 Sep 15.
IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.
Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn's disease, n=421 UC and 243 controls) in the Mount Sinai Crohn's and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts.
bMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time.
Transcriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.
IBD 的治疗方法正在向更深层次的缓解发展。疾病的分子指标可能会增加当前的终点，包括进行侵入性更小的评估的潜力。
对西奈山克罗恩病和结肠炎注册处的 712 个内镜定义的炎症（Inf）和 1778 个非炎症（Non-Inf）肠活检标本（n=498 例克罗恩病，n=421 例 UC 和 243 例对照）进行转录组分析，以确定 Inf 和 Non-Inf 活检标本之间差异表达的基因，并通过基因集方差分析生成分子炎症评分（bMIS）。使用血液转录组数据生成反映肠道分子炎症的循环 MIS（cirMIS）评分。bMIS/cirMIS 在四个独立的 IBD 队列中被验证为肠道炎症的指标。
bMIS/cirMIS 与临床、内镜和组织学疾病活动指数密切相关。具有相同组织学炎症评分的患者具有不同的 bMIS 评分，这表明 bMIS 描述了更广泛的炎症范围。在现有的临床试验数据集中，两种评分均对 IBD 治疗有反应。尽管基线内镜和组织学活动相似，但 UC 患者中基线 bMIS 水平较低的患者更有可能成为治疗反应者，而基线 bMIS 水平较高的患者则不然。最后，在处于内镜和组织学缓解的 UC 患者中，bMIS 水平较低的患者随着时间的推移不太可能出现疾病复发。
基于转录的评分提供了一种替代的客观和更深入的肠道炎症量化方法，这可能会增强目前用于疾病监测的临床评估，并有可能预测治疗反应和疾病复发风险较高的患者。
