Distinct B Cell Subsets Changes as Potential Biomarkers of Response to Biologic Therapy in Crohn’s Disease

Abstract

Biological therapies for Crohn’s disease (CD), including infliximab, adalimumab, and vedolizumab, show variable efficacy. While some predictive biomarkers exist, data on regulatory immune cells are limited. This study examined whether baseline levels of circulating T and B cell subsets can predict response to these treatments. We recruited 43 adults with conventional treatment-resistant active CD (CDAI > 330) and 16 healthy controls. Blood samples were analysed by flow cytometry at baseline (week 0) and after induction therapy (week 12 or 14, depending on the received drug) to measure T and B cell subsets and correlate them with disease activity. CD patients at baseline showed a significantly reduced frequency of memory B cells, CD5+CD1d+ B cells, plasmablasts, and transitional B cells. Additionally, significant negative correlations were identified between transitional B cells and calprotectin/platelets, and between CD5+CD1d+ B cells and calprotectin. All CD patients responded clinically to biologic therapy. In those treated with infliximab or adalimumab, mature naïve B cells decreased, with a trend toward increased CD24hiCD27+ B cells. Adalimumab responders showed a trend toward higher CD161 expression on Tregs, while vedolizumab-treated patients had a slight increase in plasmablasts. Biologic therapies in CD revealed treatment-specific immune correlations: infliximab/adalimumab responses involved B and T cell changes linked to inflammation, while VDZ response correlated with CD4+ and CD5+CD1d+ B cells. Our study suggests that infliximab/adalimumab induction therapy in CD expands circulating CD24hiCD27+ B cells and reduces mature naïve B cells, while vedolizumab increases plasmablasts. These B-cell changes may reflect distinct mechanisms and serve as potential response biomarkers.