CHARACTERIZATION OF IMMUNE PHENOTYPES AS PREDICTIVE BIOMARKERS FOR RESPONSE TO THE α4β7 INTEGRIN BLOCKER, VEDOLIZUMAB

Abstract The etiology of inflammatory bowel disease (IBD) is unknown. However, chronic inflammation from T cell activation and its subsequent tissue damage implicated in the pathogenesis IBD. Vedolizumab (VDZ), a monoclonal antibody against α4β7 integrin that prevents homing to intestinal mucosae, has shown efficacy treating both ulcerative colitis (UC) Crohn’s (CD), with greater UC. We aimed at identifying immunophenotypic gene regulatory characteristics could predict which IBD patients will benefit VDZ therapy. Peripheral blood mononuclear cells lamina propria (PBMC LPMC) were isolated before treatment after (PBMC; between weeks 14 22). PBMCs/LPMCs stained for markers, gut receptors, other immune markers. Sorted CD4+ memory (Tmem) (Treg) underwent RNA sequencing (RNA-seq). Clinical response was defined as least two-point drop partial Mayo scores Harvey-Bradshaw (CD) indices following Using an agnostic approach flow cytometry data, we examined clustering by CytofKit related markers type responsiveness. performed differential analysis (DEseq2) RNA-seq data on populations periphery propria. In total, 71 enrolled 37 received VDZ. Of patients, responded (37.8%); 21% UC 16% CD patients. A cohort responsive long term therapy, despite initial refractoriness, identified. Unsupervised revealed largest differences ileal colonic biopsies, regardless subtype or state. Likewise, cells, Tmems Tregs, showed greatest number DEGs types. who VDZ, biomarkers able response. Specific clusters found either specific state independent Tissue-related immunophenotypes signatures subsets, especially offered best predictors response, compared blood. changes PBMC expression After treatment, UC, saw increase α4β7+ also positive CCR9 marker. peripheral decrease pathway Tregs. results show profiling better represents than combination clinical immunophenotyping, allows more comprehensive view mucosal These may allow rational use given safety profile.