IM03 - A Multi-Modal Tool for Differential Diagnosis of Feline IBD and EATL Using Minimally Invasive Specimens

Abstract:

Background: Differentiating feline IBD from enteropathy-associated T-cell lymphoma (EATL) remains challenging. Invasive methods and non-specific clinical signs all present significant barriers to an accurate diagnosis. We identified over 127 potential discriminatory biomarkers from whole blood. We present here the preliminary validation of a multi-modal platform to distinguish between IBD or EATL.

Methods: Whole blood, serum, and feces were collected from client-owned cats with histopathology confirmed IBD (n=30), EATL (n=30), and healthy controls (n=10). We employed sequencing for total RNA (RNA-seq), small RNAs (smRNA-seq), 16S rRNA, and enzymatic methyl sequencing (EM-seq) to identify potential disease-related signatures for half of the cohort and validation of biomarkers for the other half. A logistic regression model, based on the methylation and gene expression profiling, was used to assess the probability of a patient having IBD or lymphoma.

Results: Multi-omic profiling revealed distinct transcriptomic and epigenetic signatures from whole blood that potentially discriminate histopathology confirmed IBD from EATL. The majority of affected genes were associated with inflammatory response, cell adhesion, and/or cell migration. The potential biomarkers identified from RNA-seq or EM-seq data showed significant differences between non-disease versus IBD versus EATL. Integration of RNA-seq and EM-seq data showed consistent patterns for a subset of the upregulated genes or downregulated genes selected for validation. We validated the identified biomarkers and established a non-“omics” approach that discriminates between IBD versus EATL.

Conclusion: Evaluation of minimally invasive specimens hold promise for distinguishing feline IBD and EATL. Ongoing work aims to further validate putative biomarkers in a prospective study.