The clinical presentation and course of Crohn's disease (CD) is highly variable.
Dr Matthew Weiser and colleagues sought to better understand the cellular and molecular mechanisms that guide this heterogeneity, and characterized the cellular processes associated with disease phenotypes.
The researchers examined both gene expression and gene regulation in non-inflamed colon tissue from a cohort of adult patients with CD and control patients.
To support the generality of our findings, the team analyzed previously published expression data from a large cohort of treatment-naïve pediatric CD and control ileum.
The research team found that adult patients with CD clearly segregated into 2 classes based on colon tissue gene expression—one that largely resembled the normal colon, and 1 where certain genes showed expression patterns normally specific to the ileum.
These classes were supported by changes in gene regulatory profiles observed at the level of chromatin accessibility, reflective of a fundamental shift in underlying molecular phenotypes.
The team observed that gene expression from the ilea of a treatment-naïve cohort of pediatric patients with CD could be similarly subdivided into colon-like and ileum-like classes.
Finally, expression patterns within these CD subclasses highlight large-scale differences in the immune response and aspects of cellular metabolism, and were associated with multiple clinical phenotypes describing disease behaviour, including rectal disease and need for colectomy.
Dr Weiser's team comments, "Our results strongly suggest that these molecular signatures define 2 clinically relevant forms of CD irrespective of tissue sampling location, patient age or treatment status."