RT Journal Article
SR Electronic
T1 CD19-CAR T-cell therapy induces deep tissue depletion of B cells
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP ard-2024-226142
DO 10.1136/ard-2024-226142
A1 Tur, Carlo
A1 Eckstein, Markus
A1 Velden, Joachim
A1 Rauber, Simon
A1 Bergmann, Christina
A1 Auth, Janina
A1 Bucci, Laura
A1 Corte, Giulia
A1 Hagen, Melanie
A1 Wirsching, Andreas
A1 Grieshaber-Bouyer, Ricardo
A1 Reis, Petra
A1 Kittan, Nicolai
A1 Wacker, Jochen
A1 Rius Rigau, Aleix
A1 Ramming, Andreas
A1 D’Agostino, Maria-Antonietta
A1 Hartmann, Arndt
A1 Müller, Fabian
A1 Mackensen, Andreas
A1 Bozec, Aline
A1 Schett, Georg
A1 Raimondo, Maria Gabriella
YR 2024
UL http://ard.bmj.com/content/early/2024/09/11/ard-2024-226142.abstract
AB Objectives CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.Methods Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages.Results Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19+ and CD20+ B cells were completely depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells and macrophages in the lymph nodes remained unchanged. Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX. Non-lymphoid organs were completely depleted of B cells.Discussion This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy.All data relevant to the study are included in the article or uploaded as online supplemental information.