Inflammatory bowel disease (IBD) treatments, such as vedolizumab, target inflammatory pathways to manage conditions like Crohn’s disease and ulcerative colitis. Vedolizumab is a monoclonal antibody that blocks integrin α4β7, preventing specific immune cells from migrating into the gut. This approach aims to reduce gut inflammation by limiting the accumulation of inflammatory cells in the intestinal lining. Although vedolizumab can achieve and maintain clinical remission in some IBD patients, only a subset fully benefits from it, highlighting an urgent need for deeper insights into why treatment sometimes fails and to develop more personalised approaches.
This study investigated how vedolizumab affects the immune cells circulating in the blood, particularly focusing on which patients responded well to the therapy. Multimodal profiling techniques revealed substantial changes in both innate and adaptive immune cell types during treatment. Notably, circulating CD4+ T cells exhibited significant alterations, with certain subsets, especially Ki67+ memory CD4+ T cells, being more abundant in patients who did not respond to vedolizumab. These T cells, which express homing receptors that guide them to inflamed gut tissue, were activated and expressed specific inflammatory markers, potentially playing a role in resistance to treatment.
Additionally, changes in proinflammatory serum proteins after vedolizumab treatment aligned with the increased presence of various immune cell populations in the bloodstream. This suggests that vedolizumab may lead to an accumulation of inflammatory cells in the blood rather than the gut, possibly contributing to the observed treatment resistance in some patients.
While the study’s insights are promising, it acknowledges limitations such as a small sample size and the need for additional data to confirm findings. Despite this, the results provide a foundation for developing biomarkers that could predict vedolizumab response. Future large-scale studies could further validate these findings and lead to the development of blood tests to identify patients most likely to benefit from vedolizumab, enabling more personalised, effective IBD management.
Reference
Horn V et al. Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4+ T cells as predictors for response to integrin α4β7-blocking therapy in inflammatory bowel disease. Gastroenterology. 2024;DOI:10.1053/j.gastro.2024.09.021.
