Single-cell characterization of peripheral blood mononuclear cells from Crohn’s disease patients on vedolizumab

Abstract

AbstractBackground & AimsVedolizumab (VDZ) is a monoclonal antibody approved for the treatment of Crohn’s disease (CD) by abrogating the gut-homing behavior of various leukocytes. Despite its efficacy, non-response to VDZ is common in clinical practice. Here, we performed an observational case-control study to interrogate the differences between responders and non-responders to VDZ during treatment.MethodsCD patients on VDZ treatment were classified as steroid-free responder or non-responder based on endoscopic-(≥3 drop in Simple Endoscopic Score for Crohn’s Disease (SES-CD)), biochemical (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin) and/or clinical response criteria (≥3 point drop in Harvey-Bradshaw Index (HBI)) during which peripheral blood was collected. Peripheral blood mononuclear cells (PBMCs) were isolated from a cohort of four responders and four non-responders which were then subjected to single-cell RNA-sequencing (scRNAseq) and mass cytometry by time of flight (CyTOF) analyses.ResultsThe most prominent differences between responders and non-responders were observed in the T and myeloid compartment, which were more and less abundant, respectively, among non-responders. T cells from non-responders generally presented lower expression of inhibitors of the NFкB signaling pathway. Abundance-wise, a lower concentration of plasmacytoid dendritic cells (pDCs) was observed among non-responders, which could be correlated with a higher abundance of pDCs in lesional tissue based on a public dataset. Classical monocytes presented an different transcriptome, with non-responders presenting lower expression of genes involved in wound-healing and cytokine-cytokine receptor signaling.ConclusionsNon-response to VDZ during treatment is associated with differences in abundance and expression of the T and myeloid compartment.