P0062 Circulating immune cell populations as predictive markers of vedolizumab response in Crohn disease
I Soleto, C González-de Castro, E Arribas, C Ramirez, M Baldan-Martin, S Riestra, A J Lucendo, M J García, E Martín-Arranz, Á De Prado, M J Casanova, M Chaparro, D Bernardo, J P Gisbert,Abstract
Background
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, with a globally rising incidence. It may result from a complex interaction among genetic predisposition, environmental influences, and alterations in gut microbiota, leading to dysregulation of both innate and adaptive immune responses. Despite advances in understanding CD, the precise immunological mechanisms underlying this disease remain unclear. Currently, biological therapies, such as vedolizumab, are among the most effective options for inducing clinical remission and controlling inflammation in CD. However, approximately two-thirds of patients do not respond adequately to these treatments. Consequently, it is essential to identify immune cell populations that can predict clinical responses to vedolizumab, facilitating more personalized treatment selection for each patient.
Methods
We characterized peripheral blood mononuclear cells (PBMCs) using spectral flow cytometry with a panel of 40 markers in patients with CD, both before and after 14 weeks of treatment with vedolizumab. Patients were categorized as responders or non-responders based on their SES-CD.
Results
At baseline Hierarchical phenotypic analysis revealed a total of 39 unique subsets of immune cells within PBMCs (Figure 1). The main populations included T cells (66%), monocytes (0.25%), B cells (12%), and natural killer cells (11%). Within the T cell group, CD4+ cells were twice as prevalent as CD8+ cells. In our evaluation of conventional dendritic cells percentages, we noted an increase in this subset within the responder group, contrasting with the trend observed in macrophages. Furthermore, an unsupervised analysis applying dimensionality reduction algorithms identified 59 clusters (Figure 2), with 37 of them showing differences when comparing responder and non-responder patients. Interestingly, no differences were observed between pre-treatment and post-treatment samples.
Conclusion
This study presents the first immunophenotyping analysis in CD patients, comparing responders and non-responders to vedolizumab based on SES-CD and highlighting differences between these groups. For the first time, these results reveal circulating immune populations as potential predictors of response to vedolizumab. Although these findings should be validated in a larger cohort to assess their clinical significance in identifying patients most likely to benefit from each therapeutic approach, they open the possibility for changes in clinical practice.