Abstract

Vitamin D downregulates the in vitro expression of the gut-tropic integrin a4ß7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease (IBD) is unclear. We tested the hypothesis that vitamin D is associated with a4ß7 immunophenotypes and risk of vedolizumab (anti- a4ß7) failure in IBD.We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry (CyTOF) in vedolizumab-naïve patients with IBD (N=48). We analyzed whole-genome mucosal gene expression (GSE73661) from GEMINI I and GEMINI long-term safety (LTS) to determine the association between vitamin D receptor (VDR) and integrin alpha-4 (ITGA4) and beta-7 (ITGB7) genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort (N= 252) with logistic regression.Immunophenotyping revealed that higher 25(OH)D was associated with decreased a4ß7+ peripheral blood mononuclear cells (R = -0.400, P < 0.01) and a4ß7+ intestinal leukocytes (R = -0.538, P= 0.03). Serum 25(OH)D was inversely associated with a4ß7+ peripheral B cells and natural killer (NK) cells and a4ß7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25(OH)D < 25 ng/mL was associated with increased vedolizumab primary non-response during induction (OR 26.10, 95% CI 14.30-48.90, P<0.001) and failure at 1-year follow-up (OR 6.10, 95% CI 3.06-12.17, P<0.001).Low serum 25(OH)D is associated with a4ß7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD.

View details for DOI 10.1093/ecco-jcc/jjab114

View details for PubMedID 34180967