Down-regulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful treatment with rituximab
Down-regulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful treatment with rituximab
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DOI：
10.1093/rheumatology/keh443
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发表时间：
2005-02-01
期刊：
影响因子：
5.5
通讯作者：
Tanaka, Y
中科院分区：
文献类型：
--
作者：
Tokunaga, M;Fujii, K;Tanaka, Y
目标.系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是自身反应性T细胞和多克隆激活的B细胞产生自身抗体。对5例常规免疫抑制剂治疗无效的SLE患者进行抗CD 20抗体（利妥昔单抗）治疗，观察其临床表现和实验室检查，包括B细胞表型分析。5例SLE患者接受利妥昔单抗（375 mg/m2）每周一次给药，共2周，这些患者在强化治疗后仍出现严重临床表现。利妥昔单抗导致意识障碍、癫痫发作、进行性感觉障碍、溶血危象、心脏功能和实验室数据等临床表现的快速改善（数天内）。1例患者的疗效持续20个月，其他患者的缓解期超过6个月。流式细胞术分析显示，利妥昔单抗治疗1周后，CD 19阳性B细胞表面CD 40和CD 80表达下调，其中2例患者的下调持续时间超过7个月。我们的初步研究提供了足够的证据证明利妥昔单抗治疗难治性SLE具有良好的耐受性和高疗效。利妥昔单抗不仅降低B细胞数量和IgG水平，而且下调B细胞上的CD 40和CD 80，表明可能通过这些共刺激分子干扰T细胞活化。B细胞数量和质量的减少表明利妥昔单抗可以改善难治性系统性红斑狼疮患者的病程。
Objectives. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T cells and polyclonally activated B cells that produce autoantibodies. Five SLE patients who failed to respond to conventional immunosuppressants were treated with anti-CD20 antibody (rituximab) and their clinical manifestations and laboratory data were evaluated, including phenotypic analysis of B cells.Methods. Rituximab (375 mg/m(2)) was administered weekly for 2 weeks in five SLE patients who developed severe manifestations despite intensive treatment.Results. Rituximab resulted in rapid improvement (within several days) in clinical manifestations such as consciousness disorder, seizures, progressive sensory disorder, haemolytic crisis, cardiac function and laboratory data. The effects lasted 20 months in one patient; other patients were in remission for more than 6 months. Flow cytometric analysis revealed down-regulation of CD40 and CD80 expression on CD19-positive B cells 1 week after infusion of rituximab, and such down-regulation was seen for more than 7 months in two patients.Conclusions. Our pilot study provides sufficient evidence of excellent tolerability and high efficacy of rituximab therapy in refractory SLE. Rituximab not only reduced B-cell number and IgG levels but down-regulated CD40 and CD80 on B cells, suggesting possible disturbance of T-cell activation through these costimulatory molecules. Reduction of both quantity and quality of B cells suggests that rituximab could improve the disease course in patients with refractory SLE.