ABSTRACT A recent New England Journal of Medicine report described the first successful use of anti‐CD19 CAR‐T cell therapy in a patient with multirefractory ulcerative colitis (UC). This exceptional case provides striking proof of concept that B cells and plasma cells can act as key pathogenic drivers in UC. In that case, the rationale for B‐cell targeting was the presence of autoantibodies against colonic αvβ6‐integrin, which disrupt activation of the anti‐inflammatory TGF‐β pathway. In other immune‐mediated diseases, although monoclonal antibodies against CD19 or CD20 have shown limited efficacy—largely due to incomplete depletion of tissue‐resident B cells and plasma cells within mucosal niches—CAR‐T cells demonstrate superior tissue penetration and more profound depletion. Although the procedure remains intensive, costly, and associated with potentially severe adverse effects, its success rekindles interest in the humoral axis of UC pathogenesis. Beyond this singular case, it encourages the exploration of safer, more scalable B‐cell–directed strategies, for patients with antibody‐driven disease. This viewpoint discusses the implications of the NEJM report and outlines future directions for therapeutic developments in inflammatory bowel diseases.
Chkolnaia et al. (Mon,) studied this question.