Single-Cell and Spatial Multi-Omics Highlight Effects of Anti-Integrin Therapy Across Cellular Compartments in Ulcerative Colitis

This is a focused, nested case-control study within our larger cohort "Immunoprofiling of the Blood and Intestine and Creation of a Gut Cell Atlas". This sub-study is titled as "Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis”. We examined the impact of Vedolizumab (VDZ), an anti-integrin antibody therapy, on the cellular landscape of ulcerative colitis (UC). While VDZ is primarily recognized for its role in preventing lymphocyte migration to the gut, the extent of its influence on other cellular populations has not been fully characterized. We used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to profile cells from both the blood and colon tissue samples. We pooled single-cell suspensions together before running scRNA-seq and CITE-seq, and subsequently deconvoluted the samples using the freemuxlet and demuxlet algorithms and variant call files (vcf) from bulk RNA-seq. This allowed us to assign cells to individual study subjects. We compared the cellular compositions of healthy individuals to those of UC patients undergoing treatment with VDZ or mesalamine (5-aminosalicylic acid/5-ASA). Our results revealed that VDZ induces significant changes in the variety and dynamics of mononuclear phagocytes within both the bloodstream and intestinal tissue, accompanied by subtle variations in lymphocyte populations. The dbGaP submission will provide raw sequencing data and participant phenotype data regarding disease and treatment status. ]]>
There were a total of 12 study participants. For prospective sample collection, patients undergoing colonoscopy or sigmoidoscopy for standard of care indications were screened for study eligibility. All participating patients gave written informed consent and approval. Peripheral blood and cold forceps biopsy samples were obtained from patients with UC, and individuals without inflammatory bowel disease (IBD), referred to as “healthy controls” (HC). Inclusion criteria were scheduled endoscopy or gastrointestinal (GI) surgical procedure for clinical purposes, males or females of any age, and mental capacity to give informed consent for study participation. For this sub-study, we recruited 4 HC, 4 patients with UC on 5-ASA therapy, and 4 patients with UC in the maintenance phase of Vedolizumab treatment. Exclusion criteria were any contraindication to endoscopic forceps biopsy such as anticoagulation or dual antiplatelet agents that are not held prior to the procedure or other high risk of bleeding. Subjects with anticipated procedural difficulty such as significant co-morbidities, prior difficult endoscopy, or any other planned high-risk endoscopic procedure (such as endoscopic mucosal resection), were also excluded to minimize risk.]]>