PT  - JOURNAL ARTICLE
AU  - Tur, Carlo
AU  - Eckstein, Markus
AU  - Velden, Joachim
AU  - Rauber, Simon
AU  - Bergmann, Christina
AU  - Auth, Janina
AU  - Bucci, Laura
AU  - Corte, Giulia
AU  - Hagen, Melanie
AU  - Wirsching, Andreas
AU  - Grieshaber-Bouyer, Ricardo
AU  - Reis, Petra
AU  - Kittan, Nicolai
AU  - Wacker, Jochen
AU  - Rius Rigau, Aleix
AU  - Ramming, Andreas
AU  - D’Agostino, Maria-Antonietta
AU  - Hartmann, Arndt
AU  - Müller, Fabian
AU  - Mackensen, Andreas
AU  - Bozec, Aline
AU  - Schett, Georg
AU  - Raimondo, Maria Gabriella
TI  - CD19-CAR T-cell therapy induces deep tissue depletion of B cells
AID  - 10.1136/ard-2024-226142
DP  - 2024 Aug 16
TA  - Annals of the Rheumatic Diseases
PG  - ard-2024-226142
4099  - http://ard.bmj.com/content/early/2024/09/11/ard-2024-226142.short
4100  - http://ard.bmj.com/content/early/2024/09/11/ard-2024-226142.full
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.