P017 Transcriptional characterization of lymphocytic colitis and comparison to collagenous colitis

Koch, S.(1);Münch, A.(2);Escudero-Hernández, C.(1,3);

(1)Linköping University, Department of Biomedical and Clinical Sciences BKV, Linköping, Sweden;(2)Linköping University, Department of Biomedical and Clinical Sciences BKV- Department of Gastroenterology and Hepatology- and Department of Health- Medicine- and Caring Sciences, Linköping, Sweden;(3)Current address: Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein- Kiel- Germany, Institute for Clinical Molecular Biology- IKMB, Kiel, Germany;


Lymphocytic colitis (LC) is an inflammatory disease of the large intestine that causes chronic, watery, non-bloody diarrhoea. LC is characterized by infiltration of lymphocytes in the colonic mucosa. To better understand LC pathophysiology on a molecular level, we performed genome-wide RNA sequencing (RNA-seq) analysis on LC mucosal samples.


We collected colonic biopsies from healthy controls (Hc), and LC patients with active disease. Collagenous colitis (CC) samples were included as a separate control. Total RNA was isolated from biopsies for bulk RNA-seq. Whole-genome expression data were analysed by principal component analysis (PCA), differential gene expression (DGE), and gene-set variation analysis (GSVA) using R statistical software. Benjamini-Hochberg FDR was used to adjust p values, considering <0.05 as statistically significant. Gene-set enrichment analysis (GSEA) was performed using GSEA software and visualized in Cytoscape.


PCA of all samples identified 2 principal components that explained 65% of the transcriptional variation and separated sample groups into distinct clusters of gene expression. Subsequent analysis revealed differential expression of 5045 genes in patients with active LC compared to Hc, which were mainly involved in DNA and telomere repair, in ubiquitinylation and proteasomal degradation, response to viruses and interleukin (IL)-12 signalling according to GSEA. Compared to CC samples, we identified 384 differentially expressed genes (DEGs) with LC. Pathway analysis displayed an enrichment in cell adhesion and proliferation genes in LC, whereas DEGs related to microbial response, collagen and wound healing processes, chemotaxis, and epithelial biology (e.g. ion channels, epithelial cell proliferation) were enriched for CC samples. Estimations of infiltrating immune cells performed by GSVA indicated a possible role for professional antigen-presenting cells (i.e. macrophages and inactive dendritic cells) as well as T regulatory cells in LC pathogenesis. 


LC is a transcriptionally homogeneous disease that can be characterised by increased expression of cell adhesion and proliferation-related genes. Furthermore, our analyses confirm an elevated immune response in LC, particularly involving macrophages, dendritic and T regulatory cells. Comparison of LC and CC gene expression additionally supports that these diseases are pathobiologically distinct.