Decreased microvilli length in CD patients

Decreased microvilli length, as a result of decreased expression of genes encoding key microvilli-specific products, might contribute to epithelial malfunction contributing to disease progression in patients with Crohn’s disease (CD).

Pathologist Prof. Thaddeus Stappenbeck (Washington School of Medicine at St Louis, Missouri, USA) and his team examined healthy regions of intestinal tissues from patients with CD to identify defects that might contribute to pathogenesis and chronicity of inflammatory bowel diseases [1]. Performing RNA sequencing from formalin-fixed paraffin-embedded ileal tissue sections of 36 patients with CD and 32 individuals without CD, the researchers catalogued the expression changes between inflamed and uninflamed tissues from the same patient. The researchers then developed methods to visualise an overlapping modular network of genes dysregulated in the samples and validated their findings using biopsy samples from the UNITI-2 phase 3 trial of ustekinumab for patients with CD and healthy individuals.

Using cluster analyses, the researchers found a cluster of genes encoding proteins associated with the enterocyte brush border to be significantly downregulated, leading them to investigate microvilli. A separate set of samples (3 control and 4 CD samples) was analysed by transmission electron microscopy (see Figure), in which they validated in all CD samples that the microvilli were shorter and less organised than in the control samples. The expression of microvilli genes correlated with microvilli length and endoscopy score and was also associated with response to treatment with ustekinumab. This research warrants follow-up to evaluate causality vs effect.

Figure. Electron micrograph of microvilli. Left panel, healthy control patient, right panel, microvilli from a CD patient [1]



1. Stappenbeck T et al. UEG Week 2019, Abstract LBA03.



Posted on 23 October, 20198 April, 2024