Merkt Wolfgang, Henes Jörg, Bergmann Christina, Lorenz Hanns-Martin
Medizinische Klinik V für Hämatologie, Onkologie und Rheumatologie, Sektion Rheumatologie, Universitätsklinikum Heidelberg, INF 410, 69120, Heidelberg, Deutschland.
Klinik für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland.
Z Rheumatol. 2025 Sep 1. doi: 10.1007/s00393-025-01700-5.
The treatment of fibrosing autoimmune diseases has so far shown no significant progress with respect to fibrosis. The reason for this is unclear. As in vitro and in vivo data have shown that B‑lymphocytes are not only responsible for autoantibody production but also play an important role in the activation of fibroblasts in an inflammatory event, depletion of B cells is meaningful in these fibrosing autoimmune diseases. The use of the CD20 antibody rituximab has shown some therapeutic benefits but could not decisively improve fibrosis, the prognosis-relevant complication in these diseases. This could be due to the insufficient tissue access of a soluble antibody and the resulting limited depletion of B‑lymphocytes in the inflammatory area of connective tissue. This is the decisive advantage of a cell-mediated destruction of autoimmune cells, which is possible via autologous B‑cell-directed chimeric antigen receptor (CAR) T‑cell therapy. The first data on the treatment of non-SLE connective tissue diseases with fibrosing aspects with autologous CAR T‑cells are developed based on this idea. This overview summarizes and discusses these data. It is important to coordinate research aspects of these experimental treatment approaches and the most important open questions, in our opinion, are proposed at the end of the review.
迄今为止,在纤维化方面,纤维化自身免疫性疾病的治疗尚未取得显著进展。其原因尚不清楚。由于体外和体内数据表明,B淋巴细胞不仅负责自身抗体的产生,而且在炎症事件中对成纤维细胞的激活也起着重要作用,因此在这些纤维化自身免疫性疾病中,B细胞的清除具有重要意义。使用CD20抗体利妥昔单抗已显示出一些治疗益处,但未能决定性地改善纤维化,而纤维化是这些疾病中与预后相关的并发症。这可能是由于可溶性抗体对组织的 access 不足以及由此导致的结缔组织炎症区域B淋巴细胞的清除受限。这就是细胞介导的自身免疫细胞破坏的决定性优势,这可以通过自体B细胞导向的嵌合抗原受体(CAR)T细胞疗法实现。基于这一理念,首次开展了关于用自体CAR T细胞治疗具有纤维化特征的非SLE结缔组织疾病的数据研究。本综述总结并讨论了这些数据。我们认为,协调这些实验性治疗方法的研究方面非常重要,并且在综述末尾提出了最重要的悬而未决的问题。
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