University Medical Center Tübingen, Postfach 2669, 72016 Tübingen, Germany.
Med Hypotheses. 2012 Apr;78(4):479-81. doi: 10.1016/j.mehy.2012.01.010. Epub 2012 Jan 30.
Although the pathogenesis of rheumatoid arthritis and other rheumatic diseases is still not fully understood, it has become clear that in many cases autoimmune responses with production of autoantibodies against physiological targets play a significant and causal role. Current immunosuppressive and immunomodulatory approaches such as bone marrow transplantation or the therapeutic antibody rituximab are effective, but unspecific and have serious side effects. Here, a method for targeted elimination of specific autoreactive B-cells which are essential for autoantibody production and maintenance of the autoimmune response is proposed. By binding to their receptive antigens linked to magnetic nanoparticles, the autoreactive B-cells can be separated from the rest of the blood in an extracorporeal filtration process, reducing the number of autoimmune cells and autoantibodies in the blood. The method can be adapted for use in different autoimmune diseases provided some key aspects of pathogenesis are known, and can be repeated if necessary. Evidence for feasibility and safety of this method is briefly reviewed, and potential limitations and hurdles to overcome are discussed.
虽然类风湿关节炎和其他风湿性疾病的发病机制仍不完全清楚，但已经清楚的是，在许多情况下，针对生理靶标的自身免疫反应产生自身抗体，起着重要的因果作用。目前的免疫抑制和免疫调节方法，如骨髓移植或治疗性抗体利妥昔单抗，虽然有效，但非特异性且有严重的副作用。在这里，提出了一种针对特异性自身反应性 B 细胞的靶向消除方法，这些细胞对于产生自身抗体和维持自身免疫反应是必需的。通过与连接到磁性纳米颗粒的受体抗原结合，自身反应性 B 细胞可以在体外过滤过程中从血液的其他部分中分离出来，从而减少血液中自身免疫细胞和自身抗体的数量。该方法可以根据发病机制的某些关键方面进行调整，适用于不同的自身免疫性疾病，如果需要，还可以重复使用。简要回顾了这种方法的可行性和安全性的证据，并讨论了潜在的局限性和需要克服的障碍。
