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Monoclonal Antibodies: New Therapeutic Agents for Autoimmune Hemolytic Anemia?

机译:单克隆抗体:自身免疫性溶血性贫血的新治疗药物?

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摘要

Conventional treatment of autoimmune hemolytic anemia (AIHA) comprises corticosteroids and splenectomy and/or other immunosuppressive drugs for refractory/relapsed patients. Monoclonal antibodies (MoAbs) rituximab and alemtuzumab have gained widespread acceptance in the management of B-cell malignancies. More recently, they have been used to treat a number of autoantibody-mediated diseases, such as both idiopathic and secondary AIHA, with encouraging results. Herein we report an overview of the medical literature on the use of MoAbs to treat AIHA. The therapeutic mechanism of action of rituximab in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus is currently a subject of considerable investigation. We have proposed that cell-associated IgG immune complexes, generated by the binding of rituximab to CD20 on B cells, may serve as decoys that attract FcγR-expressing effector cells and downregulate effector cell pathogenic action, thus reducing inflammation and tissue destruction in these diseases. We briefly review evidence that suggests that this immune complex decoy hypothesis plays a role in the therapeutic action of rituximab in AIHA, and we propose new measurements that should allow for a more complete evaluation of the importance of this mechanism in AIHA.
机译:自身免疫性溶血性贫血(AIHA)的常规治疗包括皮质类固醇和脾切除术和/或其他难治性/复发性患者的免疫抑制药物。 rituximab和alemtuzumab单克隆抗体(MoAbs)已在B细胞恶性肿瘤的治疗中得到广泛接受。最近,它们已被用于治疗许多自身抗体介导的疾病,例如特发性和继发性AIHA,取得了令人鼓舞的结果。在本文中,我们报告了有关使用MoAb治疗AIHA的医学文献的概述。利妥昔单抗在治疗自身免疫性疾病如类风湿性关节炎和狼疮中的作用的治疗机制目前是相当大的研究主题。我们已经提出,利妥昔单抗与B细胞上CD20结合产生的细胞相关IgG免疫复合物可作为诱饵,吸引FcγR表达效应细胞并下调效应细胞的致病作用,从而减少这些疾病的炎症和组织破坏。我们简要回顾了表明该免疫复合物诱饵假设在AIHA中利妥昔单抗的治疗作用中起作用的证据,并且我们提出了新的测量方法,这些方法应允许更完整地评估该机制在AIHA中的重要性。

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