Kneitz Christian, Wilhelm Martin, Tony Hans Peter
Medizinische Poliklinik der Universität Würzburg, Germany.
Immunobiology. 2002 Dec;206(5):519-27. doi: 10.1078/0171-2985-00200.
In a pilot study four patients with systemic lupus erythematosus (SLE) and autoimmune thrombocytopenia (ITP) were treated with rituximab, a B cell depicting chimeric human/mouse anti-CD20 antibody. Treatment could be performed without serious side effects and resulted in a depletion of B cells from the peripheral blood for at least 4 months. Examination of one patient three months after treatment revealed a complete depletion of B cells in the bone marrow and in the spleen as well. The time point when peripheral B cells returned into the normal range varied between 8 months and over one year and could be observed also in the spleen. The follow up over more than 12 months revealed no significant treatment-associated side effects. Total immunoglobulin and specific antibody levels did not change except for one SLE-patient receiving additional immunosuppressive treatment including cyclophosphamide because of progressive disease. Clinical effectiveness cannot be judged by the small number of patients. However, one SLE patient with refractory severe thrombocytopenia had a very Favourable response with stable platelet numbers over 100.000/microl now for more than 6 months and disappearance of anti-DNA antibodies. The treatment failure in another SLE patient could be due to the persistence of CD20-negative plasmablasts in peripheral blood which are not targeted by anti-CD20 treatment. Further studies are needed to assess the clinical benefit of B cell depletion in the treatment of autoimmune diseases.
在一项初步研究中,4例系统性红斑狼疮(SLE)合并自身免疫性血小板减少症(ITP)患者接受了利妥昔单抗治疗,利妥昔单抗是一种描绘人/鼠嵌合抗CD20抗体的B细胞。治疗过程中未出现严重副作用,外周血B细胞至少4个月持续减少。治疗3个月后对1例患者进行检查发现,其骨髓和脾脏中的B细胞也完全耗竭。外周B细胞恢复到正常范围的时间点在8个月至1年以上不等,脾脏中也可观察到这种情况。超过12个月的随访显示,未出现与治疗相关的明显副作用。除1例因疾病进展接受包括环磷酰胺在内的额外免疫抑制治疗的SLE患者外,总免疫球蛋白和特异性抗体水平未发生变化。由于患者数量较少,无法判断临床疗效。然而,1例难治性严重血小板减少症的SLE患者反应良好,血小板数量稳定在100,000/微升以上超过6个月,抗DNA抗体消失。另1例SLE患者治疗失败可能是由于外周血中持续存在抗CD20治疗无法靶向的CD20阴性浆母细胞。需要进一步研究来评估B细胞耗竭在自身免疫性疾病治疗中的临床益处。