Tur Carlo, Eckstein Markus, Velden Joachim, Rauber Simon, Bergmann Christina, Auth Janina, Bucci Laura, Corte Giulia, Hagen Melanie, Wirsching Andreas, Grieshaber-Bouyer Ricardo, Reis Petra, Kittan Nicolai, Wacker Jochen, Rius Rigau Aleix, Ramming Andreas, D'Agostino Maria-Antonietta, Hartmann Arndt, Müller Fabian, Mackensen Andreas, Bozec Aline, Schett Georg, Raimondo Maria Gabriella
Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, Erlangen, Germany; Division of Rheumatology-Fondazione Policlinico Universitario A. Gemelli, IRCCS-Università Cattolica del Sacro Cuore, Roma, Lazio, Italy.
Institute of Pathology and Comprehensive Cancer Center EMN, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
Ann Rheum Dis. 2025 Jan;84(1):106-114. doi: 10.1136/ard-2024-226142. Epub 2025 Jan 2.
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.
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.
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.
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.
靶向CD19的嵌合抗原受体（CAR）T细胞疗法可诱导自身免疫性疾病（AIDs）患者实现长期无药缓解。CD19-CAR T细胞疗法的疗效可能基于B细胞在深部组织中的耗竭；然而，这种效应尚未在人体体内得到证实。
对AIDs患者在基线时以及接受CD19-CAR T细胞治疗后进行序贯超声引导下腹股沟淋巴结活检。将结果与接受利妥昔单抗（RTX）治疗且外周血B细胞缺失的AID患者的淋巴结活检结果进行比较。对淋巴结组织进行常规染色和免疫组织化学染色，以评估组织结构以及B细胞、滤泡树突状细胞（FDC）、浆细胞、T细胞和巨噬细胞的数量。
分析了5例AID患者在CD19-CAR T细胞治疗前后以及5例接受RTX治疗后的AID患者的序贯淋巴结活检结果。此外，还分析了另外3例接受CD19-CAR T细胞治疗后的AID患者的非淋巴器官活检（结肠、肾脏和胆囊）结果。CD19-CAR T细胞治疗后淋巴结中的CD19和CD20 B细胞完全耗竭，但RTX治疗后未出现这种情况。淋巴结中的浆细胞、T细胞和巨噬细胞保持不变。CD19-CAR T细胞治疗后淋巴结中的滤泡结构被破坏，FDC耗竭，但RTX治疗后未出现这种情况。非淋巴器官中的B细胞完全耗竭。
本研究表明，CD19-CAR T细胞疗法联合标准淋巴细胞清除疗法可使AIDs患者的二级淋巴组织中的B细胞完全耗竭。
