Mass Cytometry Immunoprofiling Reveals Distinct T and B Cell Alterations Associated With Vedolizumab Response in Patients With Ulcerative Colitis

BACKGROUND Vedolizumab (VDZ) is a therapeutic antibody for ulcerative colitis (UC) that targets the α4β7 integrin, a key mediator of lymphocyte trafficking to the gut, thereby inhibiting gut homing of lymphocytes. However, its clinical efficacy remains suboptimal, with fewer than half of patients achieving long-term remission. Therefore, a deeper understanding of the immunological mechanisms of VDZ and the identification of reliable biomarkers to predict therapeutic response are therefore essential. METHODS Peripheral blood mononuclear cells from healthy controls (n = 26), patients with active UC (n = 26), VDZ non-responders (n = 8), and responders (n = 8) were analyzed by mass cytometry. Responders/non-responders were defined by endoscopic reassessment after vedolizumab induction using the Nancy histological index (≥2 = non-responders, < 2 = responders). Data were analyzed in OMIQ. RESULTS Five immune alterations were observed in VDZ responders: 1. CD4 subset cluster: α4+β7+β1∧low CD45RO+ CD62L- CD27- HLA-DR∧low CD69∧low CD38∧low CD127+ CD25∧low (TEM-like CD4+ T cells): Significantly increased vs UC active (p < 0.05). 2. IgA subset cluster: α4+β7+ β1∧int CD19∧low CD20- CD27∧low CD24- CD38+ HLA-DR+ CD69+ CD11c- IgA+ (IgA+ plasmablast-like cells): Significantly decreased vs UC active (p < 0.05). 3. IgA subset cluster: α4+β7+β1∧low CD19+ CD20+ CD11c∧high CD27- CD24- CD38- HLA-DR+ CD69+ CXCR5- IgA+ (IgA+ atypical/extrafollicular memory B cell–like cells): Significantly lower in responders vs non-responders (p < 0.05) and uniquely distinguished responders from non-responders. 4. IgG subset cluster: α4+β7∧int β1∧int CD19∧low CD20- CD27∧low CD24∧low CD38+ HLA-DR+ CD69+ CD11c- IgG+ (IgG+ plasmablast-like cells): Significantly decreased vs UC active (p < 0.05). 5. CD19 subset cluster: α4+β1+β7∧low CD19+ CD20+ CD24+ CD38- HLA-DR+ CD69+ CD27∧low CXCR5+ (memory B cell–like cells): Significantly decreased vs UC active (p < 0.05). DISCUSSION Cluster 1 (CD4 subset) likely reflects redistribution of α4β7+CD4+ T cells, predominantly TEM-like, due to VDZ-mediated gut-homing blockade and may serve as a pharmacodynamic marker. Clusters 2 (IgA subset) and 4 (IgG subset) showed decreases consistent with previously reported reduction of plasmablasts in VDZ responders, likely secondary to improved inflammation and GALT attrition. Importantly, the decrease in cluster 3 (IgA subset) represents the only immune signature that differentiates responders from non-responders. Its persistent elevation in non-responders and return to healthy control levels in responders suggest that it is a promising on-treatment biomarker for monitoring therapeutic response. These findings highlight B cell–related changes as robust predictors of treatment outcome and support their integration into precision medicine strategies for UC.