Biopsy and blood-based molecular biomarker of inflammation in IBD

Carmen Argmann, Ruixue Hou, Ryan C. Ungaro, Haritz Irizar, Zainab Al-Taie, Ruiqi Huang, Roman Kosoy, Swati Venkat, Won Min Song, Antonio F. Di'narzo, Bojan Losic, Ke Hao, Lauren Peters, Phillip H. Comella, Gabrielle Wei, Ashish Atreja, Milind Mahajan, Alina Iuga, Prerak T. Desai, Patrick BraniganAleksandar Stojmirovic, Jacqueline Perrigoue, Carrie Brodmerkel, Mark Curran, Joshua R. Friedman, Amy Hart, Esi Lamousé-Smith, Jan Wehkamp, Saurabh Mehandru, Eric E. Schadt, Bruce E. Sands, Marla C. Dubinsky, Jean Frederic Colombel, Andrew Kasarskis, Mayte Suárez-Fariñas

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Objective 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. Design 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. Results 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. Conclusion 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.

Original languageEnglish
Pages (from-to)1271-1287
Number of pages17
JournalGut
Volume72
Issue number7
DOIs
StatePublished - 1 Jul 2023

Keywords

  • IBD
  • IBD CLINICAL
  • MOLECULAR MECHANISMS
  • MOLECULAR PATHOLOGY
  • STATISTICS

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