Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn's Disease.

Area of Science:

• Gastroenterology
• Molecular Diagnostics
• Bioinformatics

Background:

• Crohn's disease (CD) management necessitates precise monitoring of disease activity and therapeutic response.
• Current monitoring methods can be invasive or lack sensitivity, highlighting the need for improved diagnostic tools.

Purpose of the Study:

• To evaluate the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic assay for patients with CD.
• To assess the ability of seRNA signatures to differentiate between active disease and remission, and to stratify disease severity.

Main Methods:

• RNA extraction and sequencing of stool samples from 68 individuals with CD across multiple time points.
• Development of random forest models to classify disease activity and severity based on seRNA signatures.
• Comparison of seRNA data with clinical metrics like the Crohn's Disease Activity Index and endoscopic findings.

Main Results:

• The seRNA classifier accurately distinguished active CD from remission (87% sensitivity, 77% specificity) and stratified mild from moderate disease (93% sensitivity, 86% specificity).
• Longitudinal analysis showed correlation between seRNA expression of therapeutic targets and lymphocyte burden with treatment response.

Conclusions:

• A novel seRNA and bioinformatics approach reliably differentiates active CD from remission and stratifies disease severity.
• This method demonstrates preliminary feasibility for predicting therapeutic response and assessing disease activity in CD patients.